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Sample records for affects bone turnover

  1. FSH Suppression Does Not Affect Bone Turnover in Eugonadal Men

    PubMed Central

    Finkelstein, Joel S.; Lee, Hang; Leder, Benjamin Z.

    2014-01-01

    Context: In vitro and animal studies have reported conflicting results regarding an independent role for FSH in the regulation of bone turnover. Objective: Our objective was to test the hypothesis that suppressing serum FSH while holding serum gonadal steroid levels stable in the eugonadal range will affect biochemical markers of bone metabolism in healthy men. Participants, Design, and Setting: Eugonadal men aged 20 to 50 years participated in this randomized controlled trial at a tertiary care academic teaching hospital. Interventions: Participants received monthly GnRH analog injections to suppress FSH secretion plus daily topical testosterone gel in prespecified doses (intervention group). Controls received matching placebos (control group). Subjects in the intervention group were individually matched with subjects in the control group to ensure that the mean testosterone and estradiol levels (measured every 4 weeks during the 16-week study period) in the 2 groups were similar. Main Outcome Measures: Biochemical markers of bone resorption (serum N-terminal telopeptide and C-terminal telopeptide), bone formation (serum osteocalcin), and FSH were measured at baseline and after 16 weeks of treatment. Results: Serum FSH declined by 2% in the control group and by 60% in the intervention group (P < .0001 for the between-group difference). Despite the substantial suppression of serum FSH in the intervention group, serum N-terminal telopeptide, C-terminal telopeptide, and osteocalcin did not change in the intervention group, nor were any between-group differences observed. Conclusion: When gonadal steroid levels are held constant, short-to midterm suppression of FSH does not affect bone turnover in men. FSH does not appear to be a significant regulator of bone metabolism in eugonadal men. PMID:24646101

  2. Bone and bone turnover.

    PubMed

    Crofton, Patricia M

    2009-01-01

    Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

  3. Altered bone turnover during spaceflight

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Morey, E. R.; Liu, C.; Baylink, D. J.

    1982-01-01

    Modifications in calcium metabolism during spaceflight were studied, using parameters that reflect bone turnover. Bone formation rate, medullary area, bone length, bone density, pore size distribution, and differential bone cell number were evaluated in growing rate both immediately after and 25 days after orbital spaceflights aboard the Soviet biological satellites Cosmos 782 and 936. The primary effect of space flight on bone turnover was a reversible inhibition of bone formation at the periosteal surface. A simultaneous increase in the length of the periosteal arrest line suggests that bone formation ceased along corresponding portions of that surface. Possible reasons include increased secretion of glucocorticoids and mechanical unloading of the skeleton due to near-weightlessness, while starvation and immobilization are excluded as causes.

  4. Bone turnover in malnourished children.

    PubMed

    Branca, F; Robins, S P; Ferro-Luzzi, A; Golden, M H

    Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting. PMID:1361595

  5. Thyroid-Stimulating Hormone Within Normal Range Does Not Affect Bone Turnover in Euthyroid Postmenopausal Women with Osteoporotic Fracture - A Preliminary Report

    PubMed Central

    Nowacki, Wieslaw; Sypniewska, Grazyna

    2011-01-01

    Background Pathogenic role of TSH suppression in the damaged bone tissue, in contrast to increased concentrations of thyroid hormones is still unknown. The aim of study was to evaluate the relationship between serum TSH and biochemical bone turnover markers in postmenopausal women with normal thyroid function and to answer whether the differences in TSH concentration within reference range may affect bone metabolism. Material and Methods 34 women (60-93 years old) admitted to the hospital after osteoporotic fracture participated in the study. Serum propeptide of type 1 procollagen (P1NP) as a bone formation marker and crosslinked C-terminal telopeptides (CTX-I), as a bone resorption marker and TSH were assayed. Results Median P1NP (p=0,05) was significantly higher in the 1st tertile of TSH values (0,35-1,88 mlU/mL). In the 3rd tertile of TSH concentrations (3,42-4,94 mlU/mL), the highest CTX-I value was found that exceed the reference range for age. No differences were found in bone markers between a group of euthyroid and a group of subjects with TSH<0,35 mlU/mL. No relationship was observed between TSH and bone formation and resorption markers in the whole group of euthyroid postmenopausal women, however bone formation was found to be in the lower reference range for age in the euthyroid subjects as well as in these with decreased TSH. Weight and BMI correlated negatively with CTX (r=-0,68 p<0,03) in fractured women in the 1st tertile of TSH. Conclusion We found no consistent evidence that TSH concentrations within reference range was associated with changes in bone turnover markers.

  6. Chronic erythroid hyperplasia and accelerated bone turnover.

    PubMed

    Weinstein, R S; Lutcher, C L

    Bone atrophy is generally thought to be the etiology of the decreased skeletal mass and fractures found in patients with ineffective hematopoiesis and associated erythroid hyperplasia. A bone biopsy from a patient with chronic erythroid hyperplasia and diffuse cortical osteopenia revealed a normal trabecular bone volume, excess osteoid, numerous osteoblasts, and increased osteoclastic resorptive surface. The increased fractional labeled surfaces and widely spaced double tetracycline labels indicated accelerated bone turnover, despite demonstrable iron deposits at the calcification front and cement lines and a low serum level of 25-hydroxyvitamin D. The relationship between the expanded marrow space and trabecular bone suggests that local marrow factors may be responsible for the rapid bone remodeling.

  7. Bone turnover markers: use in osteoporosis.

    PubMed

    Naylor, Kim; Eastell, Richard

    2012-07-01

    Biochemical markers of bone turnover (bone turnover markers, BTMs) can be used to study changes in bone remodelling in osteoporosis. Investigators and clinicians should be aware of the appropriate sample collection and storage conditions for optimum measurements of these markers. Improvements in the variability of BTM measurements have resulted from the development of assays for automated analysers, and from international consensus regarding their use. Appropriate reference intervals should be used for the optimum interpretation of results. BTMs can provide information that is useful for the management of patients with osteoporosis, for both the initial clinical assessment and for guiding and monitoring of treatment. BTMs are clinically useful to determine possible causes of secondary osteoporosis by identifying patients with high bone turnover and rapid bone loss. In the follow-up of treatment response, BTM levels respond rapidly to both anabolic and antiresorptive treatments. BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose; they are also potentially useful as surrogate biomarkers for fracture.

  8. Artificial Gravity: Effects on Bone Turnover

    NASA Technical Reports Server (NTRS)

    Heer, M.; Zwart, S /R.; Baecker, N.; Smith, S. M.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

  9. Bone Matrix Turnover And Balance In Vitro

    PubMed Central

    Flanagan, Barry; Nichols, George

    1969-01-01

    Labeled proline from incubation media has been shown to be incorporated into living bone matrix collagen in vitro. Hydroxyproline is released from fresh bone slices in similar systems in a characteristic curve against time. This hydroxyproline is derived from three distinct sources, each of which may be separately quantitated. Part of the total represents passive solubilization of matrix collagen, part is derived from new synthesis of soluble collagen occurring in vitro, and the remainder is released by cell-mediated resorptive action. The latter two processes are linear with time up to 8 hr; the former decays to zero at about 2 hr. Consequently, rates of collagen synthesis and of new collagen deposition and resorption can be quantitated simultaneously in the same system. The ability to measure these parameters of bone collagen metabolism provides methods both for the accurate evaluation of organic matrix resorption in vitro and for the accurate measurement of rates of collagen synthesis and collagen deposition. The application of the method is illustrated using parathyroid hormone and thyrocalcitonin. Parathyroid hormone diminishes collagen synthesis and stimulates collagen resorption. It reduces slightly the deposition of newly formed collagen in stable matrix. The net effect of these changes is to produce a marked negative balance. It does not significantly affect the solubility of matrix collagen. Thyrocalcitonin does not affect collagen synthesis or its deposition. It causes a marked fall in resorption rate. It has no effect on matrix collagen solubility. The net effect is to produce a marked positive balance of matrix collagen. Images PMID:5774102

  10. Bone Turnover Markers and Osteoprotegerin in Uncomplicated Pregnancy

    PubMed Central

    Styczynska, Hanna; Sobanska, Izabela; Pater, Agnieszka; Pollak, Joanna; Mankowska, Aneta

    2009-01-01

    Although calcium metabolism during pregnancy is well described the mechanisms involved in bone metabolism are not quite clear. Increase of osteoprotegerin (OPG) with elevated bone turnover is supposed to be a homeostatic mechanism limiting bone loss. The aim of the study was to assess bone turnover in pregnancy in relation to serum osteoprotegerin level. Osteocalcin (OC), beta-crosslaps (CTx), OPG, vitamin 25 OH D3, parathormone (PTH), and calcium (Ca) were determined in 30 healthy women at 1st and at 3rd trimester of pregnancy and 27 healthy age-matched non pregnant women. In pregnant women average OPG, CTx and serum calcium concentrations were found to be highly elevated. During pregnancy OPG and bone resorption significantly rised whereas only slight increase in OC level was found with concomitant decrease in serum calcium. OPG correlated positively with OC and Ca only at 1st trimester. Serum CTx and OPG at 1st trimester seemed to be the only parameters to differentiate between elevated and normal bone turnover among pregnant women. In pregnancy bone turnover increases mainly due to enhanced bone resorption. The determination of osteocalcin at the beginning of pregnancy seems to be of limited clinical use, whereas measuring bone resorption markers such as CTx and/or osteoprotegerin may have a good predictive value for later pregnancy-associated bone loss.

  11. [Bone turnover and mineralization in patients with kidney failure].

    PubMed

    James, Junichiro

    2016-09-01

    Bone remodeling is a device to accomplish "the buffering of the extracellular fluid mineral", which is one of the two major physiological functions of bone. Bone turnover is a term to express the frequency of bone remodeling, and its last step is calcification. When remodeling is induced, at first a large amount of mineral is released from bone to extracellular fluid transiently, and thereafter mineral is slowly and steadily drawn into bone. The extracellular minerals, especially calcium, are maintained by this repetition. When kidney is injured, bone turnover takes a wide spectrum from remarkably high cases to low cases. Primary calcification also shows marked individual differences. The classic renal bone diseases 5 classification clearly categorizes these disease condition, which is synonymous with renal osteodystrophy today. PMID:27561340

  12. Serum phosphorus adds to value of serum parathyroid hormone for assessment of bone turnover in renal osteodystrophy.

    PubMed

    Gentry, Jimmy; Webb, Jonathan; Davenport, Daniel; Malluche, Hartmut H

    2016-07-01

    It is well-established that parathyroid hormone (PTH) correlates with the level of bone turnover in patients with chronic kidney disease stage 5D (CKD-5D). Hyperphosphatemia is a well-established complication of end-stage renal disease and is usually attributed to dietary intake. This study evaluates the relationship between serum phosphorus levels and bone turnover in patients with CKD-5D. 93 patients with CKD-5D from the Kentucky Bone Registry who had sequentially undergone anterior iliac bone biopsies were reviewed. Undecalcified bone sections were qualitatively assessed for turnover and placed into a group with low turnover and a group with non-low (normal/high) turnover. Results of PTH and phosphorus concentrations in blood drawn at the time of biopsies were compared between the groups. PTH and phosphorus levels were significantly higher in the non-low turnover group compared to the low turnover group. Cutoff levels for PTH and phosphorus were tested for predictive power of bone turnover. Both PTH and phosphorus correlated with turnover. Adding serum phosphorus to serum PTH enhanced predictive power of PTH for low turnover. The vast majority of patients with serum phosphorus levels ≥ 6.0 mg/dL had non-low turnover, while the majority of those with low turnover had phosphorus values < 6.0 mg/dL. Classification and regression-tree analysis showed that elevated serum phosphorus (> 6.2 mg/dL) in patients with PTH < 440 pg/mL was helpful in diagnosing nonlow turnover in this range of PTH. In patients with PTH ranges of 440 - 814 pg/mL, serum phosphorus levels > 4.55 mg/dL ruled out low turnover bone disease. This suggests that not only dietary intake but also bone affects serum phosphorus levels. PMID:27191663

  13. Sclerostin as a novel marker of bone turnover in athletes

    PubMed Central

    Jóźków, P; Mędraś, M; Majda, M; Słowińska-Lisowska, M

    2016-01-01

    Sclerostin is a protein secreted by osteocytes that acts as an inhibitor of bone formation. It has been shown that physical activity affects sclerostin concentration and thus bone remodelling. The aim of the study was to evaluate serum concentrations of sclerostin, selected bone turnover markers (PTH, P1NP), 25(OH)D3 and the intake of calcium and vitamin D in physically active versus sedentary men. A total of 59 healthy men aged 17-37 were enrolled in the study (43 athletes and 16 non-athletes). The mean sclerostin concentration in the group of athletes (A) was significantly higher than in non-athletes (NA) (35.3±8.9 vs 28.0±5.6 pmol·l-1, p= 0.004). A compared with NA had higher concentrations of P1NP (145.6±77.5 vs 61.2±22.3 ng·ml-1, p= <0.0001) and 25(OH)D3 (16.9±8.4 vs 10.3±4.3 ng·ml-1, p= 0.004) and lower concentrations of PTH (25.8±8.3 vs 38.2±11.5 pg·ml-1, p= <0.0001). Vitamin D deficiency was found in 77% of A and 100% of NA. A and NA had similar daily energy intake. They did not differ as to the intake of calcium and vitamin D. We observed a negative correlation between the serum concentrations of sclerostin and calcium in the studied subjects. Our results suggest that regular, long-lasting physical training may be associated with higher concentration of sclerostin. It seems that increased sclerostin is not related to other bone turnover markers (PTH, P1NP). PMID:26929475

  14. Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

    SciTech Connect

    Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude; Malluche, Hartmut H.

    2012-01-01

    Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bone with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.

  15. Bone Growth and Turnover in Progesterone Receptor Knockout Mice

    PubMed Central

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jamie C.; Waters, Katrina M.; Lydon, John P.; O’Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-01-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence. PMID:18276762

  16. Bone turnover in prolonged critical illness: effect of vitamin D.

    PubMed

    Van den Berghe, Greet; Van Roosbroeck, David; Vanhove, Philippe; Wouters, Pieter J; De Pourcq, Lutgart; Bouillon, Roger

    2003-10-01

    In prolonged critical illness, increased bone resorption and osteoblast dysfunction have been reported facing low 25 hydroxy vitamin D [25(OH)D] concentrations. The current study investigates the extent to which lack of nutritional vitamin D and time in intensive care contribute to bone loss in the critically ill. Prolonged critically ill patients (n = 22) were compared with matched controls and then randomized to daily vitamin D supplement of either +/- 200 IU (low dose) or +/- 500 IU (high dose). At intensive care admission, serum concentrations of 25(OH)D, 1,25 dihydroxyvitamin D(3), vitamin D-binding protein, ionized calcium, IL-1, and soluble IL-6-receptor were low, and PTH was normal. Circulating type-I collagen propeptides were high, alkaline phosphatase was normal, and osteocalcin was low. Bone resorption markers [(carboxy terminal cross-linked telopeptide of type I collagen (betaCTX), pyridinoline, deoxypyridinoline (DPD)] were 6-fold increased. Serum C-reactive protein (CRP) was 40-fold, IL-6 400-fold, TNFalpha levels 5-fold, and osteoprotegerin concentrations 3-fold higher than in controls. Soluble receptor activator of nuclear factor kappaB ligand was undetectable. High-dose vitamin D only slightly increased circulating 25 hydroxy vitamin D (P < 0.05), but 1,25 dihydroxyvitamin D(3) was unaltered. High-dose vitamin D slightly increased serum osteocalcin (P < 0.05) and decreased carboxy terminal propeptide type-I collagen (P < 0.05) but did not affect other bone turnover markers. Bone-specific alkaline phosphatase, urinary pyridinoline and DPD, and serum betaCTX markedly increased with time (P < 0.01). Circulating CRP and IL-6 decreased with time, whereas TNFalpha and IL-1 remained unaltered. The fall in CRP and IL-6 was more pronounced with the high- than low-dose vitamin D (P < 0.05). Except for a mirroring of betaCTX rise by a fall in osteoprotegerin, cytokines were unrelated to the progressively aggravating bone resorption. In conclusion, prolonged

  17. Affective Disorders, Bone Metabolism, and Osteoporosis.

    PubMed

    Mezuk, Briana

    2008-12-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk.

  18. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  19. A New Insight to Bone Turnover: Role of ω-3 Polyunsaturated Fatty Acids

    PubMed Central

    López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J.

    2013-01-01

    Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κβ (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω-3 PUFA supplementation plays a major role in bone health. PMID:24302863

  20. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  1. Second-generation antipsychotics and bone turnover in schizophrenia.

    PubMed

    Okita, Kyoji; Kanahara, Nobuhisa; Nishimura, Motoi; Yoshida, Toshihiko; Yasui-Furukori, Norio; Niitsu, Tomihisa; Yoshida, Taisuke; Ishikawa, Masatomo; Kimura, Hiroshi; Nomura, Fumio; Iyo, Masaomi

    2014-08-01

    Accumulating evidence suggests that patients with schizophrenia are exposed to a high risk of osteoporosis/osteopenia caused by long-term antipsychotic treatment. The degree of bone mineral density (BMD) loss that a given antipsychotic may cause is not known. Examinations using a bone turnover marker may more accurately predict the ongoing bone states in psychiatric patients. We measured prolactin, estradiol, testosterone, and bone resorption marker (TRACP-5b) levels in 167 patients with schizophrenia and 60 normal controls. The patients showed significantly higher levels of prolactin and lower levels of TRACP-5b compared to the controls. Moreover, prolactin was negatively correlated with estradiol and testosterone in the group of all male subjects and the male patients. TRACP-5b was positively correlated with prolactin in the female patients and negatively correlated with estradiol in the group of all female subjects. The results show that the bone resorption rate was rather attenuated in the patients compared to the normal controls, suggesting a complicated etiology of BMD loss in schizophrenia patients. Several meaningful correlations between key factors in this study confirmed that hyperprolactinemia induced the suppression of sex hormones, and possibly led to the higher bone turnover. These results indicate that measurement of the resorption marker TRACP-5b might be useful to clarify the pathology of BMD loss. PMID:24888527

  2. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    PubMed

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  3. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    PubMed

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis. PMID:18037367

  4. Biochemical markers of bone turnover in osteonecrosis of the jaw in patients with osteoporosis and advanced cancer involving the bone.

    PubMed

    Cremers, Serge; Farooki, Azeez

    2011-02-01

    Osteonecrosis of the jaw (ONJ) has been hypothesized to result in part from a relative "oversuppression" of normal physiologic bone remodeling at the jaw brought about by bisphosphonate therapy. Biochemical markers of bone turnover give readily measurable information on integrated systemic bone remodeling activity, as measured by blood and urine assays. The intra- and interassay variability of most currently available assays is less than 10%, although many biological factors can influence levels of bone turnover markers. Bone turnover markers may show a dynamic response to changes in clinical status for a given disease state. Elevated bone turnover on and off treatment appears to predict adverse clinical consequences in both osteoporosis and cancer. Bisphosphonates effectively decrease the level of the bone turnover markers with a pattern depending on the marker, the bisphosphonate, the dose regimen, and the disease. However, long-term (10-year) treatment with bisphosphonates for osteoporosis does not appear to result in a progressive decline in bone turnover, as measured by markers and bone histology. The effects of long-term (greater than 2 years) treatment with monthly intravenous bisphosphonates on bone turnover markers in cancer are unknown. Discontinuation of bisphosphonate therapy appears to allow a recovery of bone turnover, which is related to the bisphosphonate, the duration of therapy, and the disease being treated. At this time, data are limited with regard to the utility of bone turnover markers in assessing risk for ONJ and whether bone marker-directed bisphosphonate holidays would be useful in prevention or treatment of ONJ.

  5. Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups

    PubMed Central

    Redmond, Jean; Fulford, Anthony J.; Jarjou, Landing; Zhou, Bo; Prentice, Ann

    2016-01-01

    Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country). Interventions: Observational study with sample collection every 4 hours for 24 hours. Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss. PMID:27294326

  6. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.

    PubMed

    Wensel, Terri M; Iranikhah, Maryam M; Wilborn, Teresa W

    2011-05-01

    Osteoporosis is a degenerative bone disease affecting approximately 10 million American adults. Several options are available to prevent development of the disease or slow and even stop its progression. Nonpharmacologic measures include adequate intake of calcium and vitamin D, exercise, fall prevention, and avoidance of tobacco and excessive alcohol intake. Current drug therapy includes bisphosphonates, calcitonin, estrogen or hormone therapy, selective estrogen receptor modulators, and teriparatide. Denosumab, a receptor activator of nuclear factor-K B ligand (RANKL) inhibitor, was recently approved by the United States Food and Drug Administration for treatment of postmenopausal osteoporosis. Patients treated with denosumab experienced significant gains in bone mineral density, rapid reductions in markers of bone turnover, and a reduced risk for new vertebral fracture. Compared with placebo, patients receiving denosumab 60 mg subcutaneously once every 6 months experienced gains in bone mineral density of 6.5-11% when treated for 24-48 months. One trial demonstrated the superiority of denosumab compared with alendronate, but the differences were small. The most common adverse reactions to denosumab include back pain, pain in extremities, musculoskeletal pain, and cystitis. Serious, but rare, adverse reactions include the development of serious infections, dermatologic changes, and hypocalcemia. The recommended dosing of denosumab is 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Although beneficial effects on bone mineral density and fracture rate have been established in clinical trials, the risks associated with denosumab must be evaluated before therapy initiation. Of concern is the risk of infection, and denosumab should likely be avoided in patients taking immunosuppressive therapy or at high risk for infection. Therefore, bisphosphonates will likely remain as first-line therapy. Denosumab should be considered in

  7. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    NASA Technical Reports Server (NTRS)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  8. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    PubMed Central

    Westerlind, Kim C.; Wronski, Thomas J.; Ritman, Erik L.; Luo, Zong-Ping; An, Kai-Nan; Bell, Norman H.; Turner, Russell T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain. PMID:9108129

  9. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    PubMed

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  10. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    PubMed

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover. PMID:24126694

  11. RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

    PubMed

    Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

    2016-10-01

    Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism. PMID:27328677

  12. RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

    PubMed

    Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

    2016-10-01

    Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

  13. Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment

    PubMed Central

    Akel, Nisreen S.; Vander Schilden, Jaclyn; Bacon, Anthony W.; Bracey, John W.; Sowder, Timothy; Skinner, Robert A.; Swain, Frances L.; Hogue, William R.; Leblanc, Donna B.; Gaddy, Dana; Wenger, Galen R.; Suva, Larry J.

    2012-01-01

    Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients’ age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population. PMID:22916188

  14. Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state

    PubMed Central

    Gossiel, Fatma; Finigan, Judith; Jacques, Richard; Reid, David; Felsenberg, D; Roux, Christian; Glueer, Claus; Eastell, Richard

    2014-01-01

    In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30–39 years (n=258) and women aged 55–79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age. PMID:25228986

  15. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.

    PubMed

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  16. Bone GLA protein (BGP) levels and bone turnover in rheumatoid arthritis.

    PubMed

    Magaro, M; Altomonte, L; Mirone, L; Zoli, A; Corvino, G

    1989-06-01

    Bone GLA protein (BGP) and other biochemical indices of bone turnover were measured in 42 female patients with rheumatoid arthritis (RA) and in a group of normal subjects matched for sex and age. Mean serum BGP concentrations were significantly higher in patients with active arthritis than in patients with mild activity (p less than 0.01) and controls (p less than 0.01). No significant difference was found in serum BGP levels and in other parameters of bone turnover when the patients were stratified according to functional class or duration of disease. There was a correlation between BGP and alkaline phosphatase levels only in RA patients with high activity of disease. Our data suggest an accelerated bone turnover in patients with active RA. We infer that in such patients the impairment of bone metabolism is a determinant of RA-associated osteopenia. Disease activity rather than functional impairment or duration of arthritis should be regarded as a factor in the bone loss of RA.

  17. Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

    PubMed

    Morabito, Nunziata; Catalano, Antonino; Gaudio, Agostino; Morini, Elisabetta; Bruno, Lucia Maria; Basile, Giorgio; Tsiantouli, Eleni; Bellone, Federica; Agostino, Rita Maria; Piraino, Basilia; La Rosa, Maria Angela; Salpietro, Carmelo; Lasco, Antonino

    2016-09-01

    Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels. PMID:26204844

  18. A 12-month prospective study of the relationship between stress fractures and bone turnover in athletes.

    PubMed

    Bennell, K L; Malcolm, S A; Brukner, P D; Green, R M; Hopper, J L; Wark, J D; Ebeling, P R

    1998-07-01

    Bone remodeling may be involved in the pathogenesis of stress fractures in athletes. We conducted a 12-month prospective study to evaluate bone turnover in 46 female and 49 male track and field athletes aged 17-26 years (mean age 20.3; SD 2.0) 20 of whom developed a stress fracture. Baseline levels of bone turnover were evaluated in all athletes and monthly bone turnover levels were evaluated in a subset consisting of the 20 athletes who sustained a stress fracture and a matched comparison group who did not sustain a stress fracture. Bone formation was assessed using serum osteocalcin (OC) measured by human immunoradiometric assay and bone resorption by urinary excretion of pyridinium cross-links (Pyr and D-Pyr); high performance liquid chromatography and N-telopeptides of type 1 collagen (NTx) using ELISA assay. Athletes who developed stress fractures had similar baseline levels of bone turnover compared with their nonstress fracture counterparts (P > 0.10). Results of serial measurements showed no differences in average levels of Pyr, D-Pyr, or OC in those who developed stress fractures (P = 0.10) compared with the control group. In the athletes with stress fractures, there was also no difference in bone turnover levels prior to or following the onset of bony pain. Our results show that single and multiple measurements of bone turnover are not clinically useful in predicting the likelihood of stress fractures in athletes. Furthermore, there were no consistent temporal changes in bone turnover associated with stress fracture development. However, our results do not negate the possible pathogenetic role of local changes in bone remodeling at stress fracture sites, given the high biological variability of bone turnover markers and the fact that levels of bone turnover reflect the integration of all bone remodeling throughout the skeleton. PMID:9632851

  19. Lack of seasonal variation in bone mass and biochemical estimates of bone turnover

    SciTech Connect

    Overgaard, K.; Nilas, L.; Johansen, J.S.; Christiansen, C.

    1988-01-01

    Three previous studies have indicated a seasonal variation in bone mineral content, with values during the summer being 1.7% to 7.5% higher than during the winter. We have examined the seasonal influence on both bone mass, biochemical estimates of bone turnover and vitamin D metabolites in 86 healthy women, aged 29-53 years. All participants were followed up for 2 years with examinations every 6 weeks or 3 months. Bone mineral content in the proximal and distal part of the forearm (single photon absorptiometry) did not reveal any significant seasonal variation, whereas bone mineral density of the lumbar spine (dual photon absorptiometry) indicated that the highest values occurred in winter. None of the biochemical parameters showed any statistically significant cyclical changes. Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D3 showed a highly significant seasonal variation, whereas the serum 1,25-dihydroxyvitamin D concentration was virtually unchanged. We conclude that seasonal variation in bone mineral content and bone turnover should not be taken into account when interpreting data from longitudinal studies of healthy pre- and postmenopausal women on a sufficient vitamin D nutriture.

  20. Assessment of age and risk factors on bone density and bone turnover in healthy premenopausal women.

    PubMed

    Hansen, M A

    1994-05-01

    The influence of age and risk factors on bone density and bone turnover was evaluated in 249 healthy premenopausal women. Risk factors were assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of caffeine, smoking habits and physical activity). Bone mineral density (BMD) measurements were obtained in the distal forearm, the lumbar spine and the proximal femur. Bone turnover were assessed by plasma bone Gla proteins (pBGP) and fasting urinary hydroxyproline corrected for creatinine (fUHPr/Cr). Peak bone density seems to be achieved before the age of 30 years, whereafter we found no appreciable bone loss at any skeletal site. Accordingly, the levels of pBGP and fUHPr/Cr were increased before the age of 30, whereafter the values stabilized at a lower level. A dairy calcium intake above 660 mg/day significantly increased BMD in the spine and proximal femur by 3%-5%. Physical activity alone had no influence on BMD, but in combination with calcium intake an additive effect was observed. Women who had an active lifestyle (corresponding to at least 1 h of daily walking) and a dairy calcium intake above 660 mg/day had a 3%-7% increase in BMD compared with more sedentary women with a calcium intake below this limit. Vitamin D supplements, caffeine, smoking and reproductive history did not consistently influence BMD or bone turnover. Only pBGP was selectively reduced by smoking and current use of oral contraceptives, respectively. We conclude that there is no appreciable change in BMD before the menopause once skeletal maturity has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats.

    PubMed

    Hirata, Junya; Hirai, Kazuya; Asai, Hirobumi; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato; Yamato, Hideyuki; Watanabe-Akanuma, Mie

    2015-10-01

    Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation-related parameters and bone resorption-related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation-related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. PMID:26112820

  2. Bone turnover in passive smoking female rat: relationships to change in bone mineral density

    PubMed Central

    2011-01-01

    Background Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat. Methods Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats. Conclusion Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat. PMID:21663694

  3. Association of bone mineral density with biochemical markers of bone turnover in hemodialysis children

    PubMed Central

    Hajizadeh, Niloofar; Mehrkash, Mehryar; Fahimi, Daryoosh; Qorbani, Mostafa; Shafa, Nina

    2016-01-01

    Introduction: Although some descriptive and cross-sectional studies have been reported about bone mass in chronic kidney disease (CKD) children, only a few studies investigated markers of bone turnover and the bone mass measurements. Objectives: The aim of this study was to evaluate the association between bone mineral density (BMD) and biochemical markers of bone turnover in hemodialysis (HD) children. Patients and Methods: The children who had received dialysis for at least the preceding 6‐month were included. BMD was measured for total body, the lumbar spine and the femoral neck and the blood samples were tested to assess biochemical bone turnover markers. Results: The study group was comprised of 27 patients with CKD, 9 males (33%) and 18 females (67%) with the mean±SD age of the subjects 14.9±4.5 years. Positive significant correlations of parathyroid hormone (PTH) with total body bone densitometry Z-score, lumbar spine and femoral neck Z-score(r=0.43, P=0.06; r=0.41, P=0.08 and r=0.45, P=0.05, respectively) was noted. In addition, positive significant correlations calcium and total body, lumbar spine and femoral neck Z-score (r=0.52, P=0.02; r=0.28, P=0.23 and r=0.36, P=0.12, respectively) was seen. Interestingly, a positive significant correlation between alkaline phosphatase (ALP) and lumbar spine Z-score was found (r=0.46, P=0.04), while the correlation of this parameter with total body and femoral neck Z-score was not significant (P>0.05). Conclusion: In our study, majority of patients with CKD had low level of BMD. In addition, lower levels of calcium (Ca), phosphorus (P), PTH and 25 (OH) vitamins D in patients with abnormal BMD Z-scores were detected. PMID:27689118

  4. Association of bone mineral density with biochemical markers of bone turnover in hemodialysis children

    PubMed Central

    Hajizadeh, Niloofar; Mehrkash, Mehryar; Fahimi, Daryoosh; Qorbani, Mostafa; Shafa, Nina

    2016-01-01

    Introduction: Although some descriptive and cross-sectional studies have been reported about bone mass in chronic kidney disease (CKD) children, only a few studies investigated markers of bone turnover and the bone mass measurements. Objectives: The aim of this study was to evaluate the association between bone mineral density (BMD) and biochemical markers of bone turnover in hemodialysis (HD) children. Patients and Methods: The children who had received dialysis for at least the preceding 6‐month were included. BMD was measured for total body, the lumbar spine and the femoral neck and the blood samples were tested to assess biochemical bone turnover markers. Results: The study group was comprised of 27 patients with CKD, 9 males (33%) and 18 females (67%) with the mean±SD age of the subjects 14.9±4.5 years. Positive significant correlations of parathyroid hormone (PTH) with total body bone densitometry Z-score, lumbar spine and femoral neck Z-score(r=0.43, P=0.06; r=0.41, P=0.08 and r=0.45, P=0.05, respectively) was noted. In addition, positive significant correlations calcium and total body, lumbar spine and femoral neck Z-score (r=0.52, P=0.02; r=0.28, P=0.23 and r=0.36, P=0.12, respectively) was seen. Interestingly, a positive significant correlation between alkaline phosphatase (ALP) and lumbar spine Z-score was found (r=0.46, P=0.04), while the correlation of this parameter with total body and femoral neck Z-score was not significant (P>0.05). Conclusion: In our study, majority of patients with CKD had low level of BMD. In addition, lower levels of calcium (Ca), phosphorus (P), PTH and 25 (OH) vitamins D in patients with abnormal BMD Z-scores were detected.

  5. Is Bone Tissue Really Affected by Swimming? A Systematic Review

    PubMed Central

    Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

    2013-01-01

    Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

  6. [Clinical usefulness of bone turnover markers in the management of osteoporosis].

    PubMed

    Yano, Shozo

    2013-09-01

    Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future. PMID:24369600

  7. Biological and within-subject variability of calcium kinetics and biochemical markers of bone turnover

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone loss is a critical issue during space flight. Evaluating changes in bone and calcium metabolism in astronauts often requires multiple preflight data collection points. Bone turnover and calcium kinetics were measured in 4 healthy subjects, and the day-to-day and between-subject variations were ...

  8. The use of Na-22 as a tracer for long-term bone mineral turnover studies.

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.; Rieksts, G. A.; Palmer, R. F.; Gillis, M. F.

    1979-01-01

    Sodium-22 has been studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with Na-22, which is released through the metabolic turnover of the bone. The Na-22 not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high, but nontoxic levels of NaCl. The Na-22 tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  9. Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax

    PubMed Central

    Yu, Lixin; Hou, Shengcai; Hu, Bin; Zhao, Liqiang; Miao, Jinbai; Wang, Yang; Li, Tong; Zhang, Zhenkui; You, Bin; Pang, Baosen; Liang, Yufang; Zhao, Yi; Hao, Wei

    2016-01-01

    Background To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Methods Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Results Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. Conclusions It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in

  10. Determinants of bone turnover markers in healthy premenopausal women.

    PubMed

    Adami, Silvano; Bianchi, Gerolamo; Brandi, Maria Luisa; Giannini, Sandro; Ortolani, Sergio; DiMunno, Ombretta; Frediani, Bruno; Rossini, Maurizio

    2008-05-01

    Bone turnover markers (BTMs) are widely used for the management of osteoporosis, and the premenopausal reference range is the target value for the treatment of postmenopausal osteoporosis with antiresorbing agents. Three serum BTMs (serum C-telopeptide of type I collagen [CTX], osteocalcin [OC], and N-terminal propeptide of type I procollagen [P1NP]), serum calcium, creatinine, phosphate, magnesium, and follicle-stimulating hormone (FSH) were measured in 638 healthy premenopausal women aged 20-50 years. In 83 women on the contraceptive pill (CP), the levels of the three BTMs adjusted for all confounding factors were 14-26% lower (P < 0.005) than in non-CP users. In 18 women considered perimenopausal for serum FSH levels >30 IU/mL despite having regular menses, BTM levels were significantly higher than in age-matched women. This group of subjects and the women on the CP were excluded from further analysis. The three BTMs significantly decreased with advancing age and were negatively and independently correlated with body mass index (P < 0.001) and serum phosphate. In conclusion, we confirm that CP use is associated with significantly lower BTM values. An increase in BTM concentrations can be observed in perimenopausal women, i.e., women with normal menses but FSH levels >30 IU/mL. BTMs decrease substantially with advancing age, and this appears to be associated with changes in body weight and serum phosphate. New normative ranges for serum OC, CTX, and P1NP were identified; and our findings in general impose a redefinition of the criteria for establishing the normal ranges for BTMs.

  11. Gonadal steroid–dependent effects on bone turnover and bone mineral density in men

    PubMed Central

    Finkelstein, Joel S.; Lee, Hang; Leder, Benjamin Z.; Goldstein, David W.; Hahn, Christopher W.; Hirsch, Sarah C.; Linker, Alex; Perros, Nicholas; Servais, Andrew B.; Taylor, Alexander P.; Webb, Matthew L.; Youngner, Jonathan M.; Yu, Elaine W.

    2016-01-01

    BACKGROUND. Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS. One hundred ninety-eight healthy men, ages 20–50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS. As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS. Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION. ClinicalTrials.gov, NCT00114114

  12. Effect of Calcitriol on Bone Turnover and Osteocalcin in Recent-Onset Type 1 Diabetes

    PubMed Central

    Napoli, Nicola; Strollo, Rocky; Pitocco, Dario; Bizzarri, Carla; Maddaloni, Ernesto; Maggi, Daria; Manfrini, Silvia; Schwartz, Ann; Pozzilli, Paolo

    2013-01-01

    Background Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of β-cell function and metabolic control was examined. Methodology/Principal Findings We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve β-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1∶1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01) while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and β-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. Conclusions Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to β-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction. PMID:23437144

  13. [Clinical usefulness of bone turnover markers with the treatment of osteoporosis].

    PubMed

    Miura, Masakazu

    2014-03-01

    Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

  14. Bone mass and bone turnover in power athletes, endurance athletes, and controls: a 12-month longitudinal study.

    PubMed

    Bennell, K L; Malcolm, S A; Khan, K M; Thomas, S A; Reid, S J; Brukner, P D; Ebeling, P R; Wark, J D

    1997-05-01

    Strain magnitude may be more important than the number of loading cycles in controlling bone adaptation to loading. To test this hypothesis, we performed a 12 month longitudinal cohort study comparing bone mass and bone turnover in elite and subelite track and field athletes and less active controls. The cohort comprised 50 power athletes (sprinters, jumpers, hurdlers, multievent athletes; 23 women, 27 men), 61 endurance athletes (middle-distance runners, distance runners; 30 women, 31 men), and 55 nonathlete controls (28 women, 27 men) aged 17-26 years. Total bone mineral content (BMC), regional bone mineral density (BMD), and soft tissue composition were measured by dual-energy X-ray absorptiometry. Bone turnover was assessed by serum osteocalcin (human immunoradiometric assay) indicative of bone formation, and urinary pyridinium crosslinks (high-performance liquid chromatography) indicative of bone resorption. Questionnaires quantified menstrual, dietary and physical activity characteristics. Baseline results showed that power athletes had higher regional BMD at lower limb, lumbar spine, and upper limb sites compared with controls (p < 0.05). Endurance athletes had higher BMD than controls in lower limb sites only (p < 0.05). Maximal differences in BMD between athletes and controls were noted at sites loaded by exercise. Male and female power athletes had greater bone density at the lumbar spine than endurance athletes. Over the 12 months, both athletes and controls showed modest but significant increases in total body BMC and femur BMD (p < 0.001). Changes in bone density were independent of exercise status except at the lumbar spine. At this site, power athletes gained significantly more bone density than the other groups. Levels of bone formation were not elevated in athletes and levels of bone turnover were not predictive of subsequent changes in bone mass. Our results provide further support for the concept that bone response to mechanical loading depends

  15. Factors affecting bone strength other than osteoporosis.

    PubMed

    Ratti, Chiara; Vulcano, Ettore; Canton, Gianluca; Marano, Marco; Murena, Luigi; Cherubino, Paolo

    2013-10-01

    Osteoporosis is the most common cause of bone fragility, especially in post-menopausal women. Bone strength may be compromised by several other medical conditions and medications, which must be ruled out in the clinical management of patients affected by fragility fractures. Indeed, 20-30% of women and up to 50% of men affected by bone fragility are diagnosed with other conditions affecting bone strength other than osteoporosis. These conditions include disorders of bone homeostasis, impaired bone remodeling, collagen disorders, and medications qualitatively and quantitatively affecting bone strength. Proper diagnosis allows correct treatment to prevent the occurrence of fragility fractures. PMID:24046057

  16. miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis.

    PubMed

    Valencia, Karmele; Martín-Fernández, Marta; Zandueta, Carolina; Ormazábal, Cristina; Martínez-Canarias, Susana; Bandrés, Eva; de la Piedra, Concepción; Lecanda, Fernando

    2013-01-01

    Recent evidence suggests that miRNAs could be used as serum markers in a variety of normal and pathological conditions. In this study, we aimed to identify novel miRNAs associated with skeletal metastatic disease in a preclinical model of lung cancer bone metastasis. We assessed the validity of these miRNAs as reliable serum biochemical markers to monitor the extent of disease and response to treatment in comparison to imaging techniques and standard biochemical markers of bone turnover. Using a murine model of human lung cancer bone metastasis after zoledronic acid (ZA) treatment, PINP (procollagen I amino-terminal propeptide) was the only marker that exhibited a strong correlation with osteolytic lesions and tumor burden at early and late stages of bone colonization. In contrast, BGP (osteocalcin) and CTX (carboxyterminal telopeptide) demonstrated a strong correlation only at late stages. We performed qPCR based screening of a panel of 380 human miRNAs and quantified bone metastatic burden using micro-CT scans, X-rays and bioluminescence imaging. Interestingly, levels of miR-326 strongly associated with tumor burden and PINP in vehicle-treated animals, whereas no association was found in ZA-treated animals. Only miR-193 was associated with biochemical markers PINP, BGP and CTX in ZA-treated animals. Consistently, miR-326 and PINP demonstrated a strong correlation with tumor burden. Our findings, taken together, indicate that miR-326 could potentially serve as a novel biochemical marker for monitoring bone metastatic progression.

  17. The osteocyte: key player in regulating bone turnover

    PubMed Central

    Goldring, Steven R

    2015-01-01

    Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell–cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading. PMID:26557372

  18. Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs.

    PubMed

    Hamed, Sherifa A

    2016-01-01

    Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

  19. Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

    NASA Technical Reports Server (NTRS)

    Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

    1997-01-01

    Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone

  20. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover.

    PubMed

    van Lierop, Antoon H; Hamdy, Neveen At; Hamersma, Herman; van Bezooijen, Rutger L; Power, Jon; Loveridge, Nigel; Papapoulos, Socrates E

    2011-12-01

    Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss-of-function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked C-telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age- and gender-matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in

  1. Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness

    PubMed Central

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    Background We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Methods Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. Results AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. Conclusions We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness. PMID:25617902

  2. Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels.

    PubMed

    Pennisi, P; Signorelli, S S; Riccobene, S; Celotta, G; Di Pino, L; La Malfa, T; Fiore, C E

    2004-05-01

    Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/-0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4 micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs 0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG-RANKL system

  3. Bone marrow ablation demonstrates that estrogen plays an important role in osteogenesis and bone turnover via an antioxidative mechanism.

    PubMed

    Shi, Chunmin; Wu, Jun; Yan, Quanquan; Wang, Rong; Miao, Dengshun

    2015-10-01

    To assess the effect of estrogen deficiency on osteogenesis and bone turnover in vivo, 8-week-old mice were sham-operated or bilaterally ovariectomized (OVX), and after 8 weeks, mechanical bone marrow ablation (BMX) was performed and newly formed bone tissue was analyzed from 6 days to 2 weeks after BMX. Our results demonstrated that OVX mice following BMX displayed 2 reversed phase changes, one phase observed at 6 and 8 days after BMX delayed osteogenesis accompanied by a delay in osteoclastogenesis, and the other phase observed at 12 and 14 days after BMX increased osteoblastic activity and osteoclastic activity. Furthermore, we asked whether impaired osteogenesis caused by estrogen deficiency was associated with increased oxidative stress, and oxidative stress parameters were examined in bone tissue from sham-operated and OVX mice and OVX mice were administrated with antioxidant N-acetyl-l-cysteine (NAC) or vehicle after BMX. Results demonstrated that estrogen deficiency induced oxidative stress in mouse bone tissue with reduced antioxidase levels and activity, whereas NAC administration almost rescued the abnormalities in osteogenesis and bone turnover caused by OVX. Results from this study indicate that estrogen deficiency resulted in primarily impaired osteogenesis and subsequently accelerated bone turnover by increasing oxidative stress and oxidative stress promises to be an effective target in the process of treatment of postmenopausal osteoporosis. PMID:26036172

  4. Sexual selection affects local extinction and turnover in bird communities

    USGS Publications Warehouse

    Doherty, P.F.; Sorci, G.; Royle, J. Andrew; Hines, J.E.; Nichols, J.D.; Boulinier, T.

    2003-01-01

    Predicting extinction risks has become a central goal for conservation and evolutionary biologists interested in population and community dynamics. Several factors have been put forward to explain risks of extinction, including ecological and life history characteristics of individuals. For instance, factors that affect the balance between natality and mortality can have profound effects on population persistence. Sexual selection has been identified as one such factor. Populations under strong sexual selection experience a number of costs ranging from increased predation and parasitism to enhanced sensitivity to environmental and demographic stochasticity. These findings have led to the prediction that local extinction rates should be higher for species/populations with intense sexual selection. We tested this prediction by analyzing the dynamics of natural bird communities at a continental scale over a period of 21 years (1975-1996), using relevant statistical tools. In agreement with the theoretical prediction, we found that sexual selection increased risks of local extinction (dichromatic birds had on average a 23% higher local extinction rate than monochromatic species). However, despite higher local extinction probabilities, the number of dichromatic species did not decrease over the period considered in this study. This pattern was caused by higher local turnover rates of dichromatic species, resulting in relatively stable communities for both groups of species. Our results suggest that these communities function as metacommunities, with frequent local extinctions followed by colonization. Anthropogenic factors impeding dispersal might therefore have a significant impact on the global persistence of sexually selected species.

  5. Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

    PubMed

    Peng, Jia; Hui, Kang; Hao, Chen; Peng, Zhao; Gao, Qian Xing; Jin, Qi; Lei, Guo; Min, Jiang; Qi, Zhou; Bo, Chen; Dong, Qian Nian; Bing, Zhou Han; Jia, Xu You; Fu, Deng Lian

    2016-07-01

    It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation. PMID:27028715

  6. Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Zhang, Yan; Lai, Wan-Ping; Leung, Ping-Chung; Wu, Chun-Fu; Yao, Xin-Sheng; Wong, Man-Sau

    2006-02-01

    The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs. OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

  7. Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Zhang, Yan; Lai, Wan-Ping; Leung, Ping-Chung; Wu, Chun-Fu; Yao, Xin-Sheng; Wong, Man-Sau

    2006-02-01

    The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs. OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis. PMID:16462034

  8. Biochemical Markers of Bone Turnover Part I: Biochemistry and Variability

    PubMed Central

    2005-01-01

    With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies has markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. Part I of this article provides an overview of the basic biochemistry of bone markers, and sources of non-specific variability. Part II (to be published in a subsequent issue of this journal) will review the current evidence regarding the clinical use of biochemical markers of bone remodelling in metabolic and metastatic bone disease. PMID:16648882

  9. Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover.

    PubMed

    Ruddle, N H; Li, C B; Horne, W C; Santiago, P; Troiano, N; Jay, G; Horowitz, M; Baron, R

    1993-11-01

    HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations.

  10. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women.

    PubMed

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  11. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

    PubMed Central

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47–78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  12. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).

    PubMed

    Tavella, Sara; Ruggiu, Alessandra; Giuliani, Alessandra; Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

    2012-01-01

    Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.

  13. Sclerostin levels and bone turnover markers in adolescents with anorexia nervosa and healthy adolescent girls.

    PubMed

    Faje, Alexander T; Fazeli, Pouneh K; Katzman, Debra K; Miller, Karen K; Breggia, Anne; Rosen, Clifford J; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

    2012-09-01

    Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13-18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r=0.67 and 0.53, p=0.0002 and 0.005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group.

  14. Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

    PubMed

    Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

    2016-01-15

    Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts.

  15. Bone Mineral Density and Bone Turnover Markers Under Bisphosphonate Therapy Used in the First Year After Liver Transplantation.

    PubMed

    Nowacka-Cieciura, Ewa; Sadowska, Anna; Pacholczyk, Marek; Chmura, Andrzej; Tronina, Olga; Durlik, Magdalena

    2016-01-01

    BACKGROUND Rapid bone loss occurs early after liver transplantation (Tx), concomitantly with intensified bone turnover. In the present study we investigated the effect of bisphosphonates (bisph) added to vitamin D (vitD) and calcium on bone mineral density (BMD) and bone biomarkers in liver graft recipients in the first posttransplant year. MATERIAL AND METHODS In 28 patients BMD was determined at the third month after Tx. In case of osteopenia (Tscore ≤-1.0) and no contraindications, oral bisph was started for 1 year (group BP, n=14); other patients served as controls (CON, n=14). The changes in BMD and biomarkers of bone formation were osteocalcin (OC), bone alkaline phosphatase (BAP), and resorption. Study endpoints were active isoform 5b of the tartrate-resistant acid phosphatase (TRACP5b), serum pyridinoline crosslinks (PYD), and urine excretion of deoxypyridinoline (Dpd) crosslinks. RESULTS In 19 (68%) patients, reduced BMD (T-score ≤1.0) was observed at baseline. The changes in lumbar BMD in BP and CON groups were 5.2% and 1.5%, respectively, not reaching statistical significance. Baseline PYD, Dpd/creat, and OC were elevated in all patients, indicating high bone turnover. We observed decrease in PYD and Dpd/creat in both groups; however, OC decreased only under bisph therapy. Increase in BAP was observed in the control group but not in the BP group. The changes in BAP and OC were significantly different (p<0.01). CONCLUSIONS Combining bisph with vitD and calcium is an effective bone- sparing strategy in liver transplant recipients in the first posttransplant year. Bisph more efficiently decreased the rate of bone turnover than vitD and calcium alone. PMID:27112626

  16. Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling.

    PubMed

    Lombardi, Giovanni; Lanteri, Patrizia; Colombini, Alessandra; Banfi, Giuseppe

    2012-02-03

    Casual or systematic errors occurring in pre-analytical, analytical or post-analytical phases influence laboratory test results. The areas where pre-analytical phase errors most often arise are: timing of specimen collection; selection of specimen type; and time and temperature of storage/transport. Bone turnover markers are clinically useful in evaluating bone metabolism. Although unquestionably valuable tools, little is known about the pre-analytical precautions for their correct use and there is no consensus on kind of sample, or storage time and temperature before analysis. Moreover, biological variability, because of uncontrollable and controllable factors, will affect pre-analytical variability. Serum should be preferred to simplify blood drawing; therefore, only one tube should be used for the analysis of all bone markers. Short-term storage at 4°C may be advisable to preserve stability, immediate storage at -70°C is recommended for longer periods, while avoiding repeated freeze-thawing cycles. Sampling should be performed in the morning in fasting subjects who have abstained from physical exercise for 24 h. This review aimed to give a knowledge update on pre-analytical phase precautions in performing bone turnover marker measurement.

  17. CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts

    PubMed Central

    Greenblatt, Matthew B.; Park, Kwang Hwan; Oh, Hwanhee; Kim, Jung-Min; Shin, Dong Yeon; Lee, Jae Myun; Lee, Jin Woo; Singh, Anju; Lee, Ki-young; Hu, Dorothy; Xiao, Changchun; Charles, Julia F.; Penninger, Josef M.; Lotinun, Sutada; Baron, Roland; Ghosh, Sankar

    2015-01-01

    Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-κB signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget’s disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-κB activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-κBα (IκBα), down-regulating ubiquitination of IκBα via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder. PMID:26195726

  18. Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women

    PubMed Central

    Bredella, Miriam A.; Gerweck, Anu V.; Barber, Lauren A.; Breggia, Anne; Rosen, Clifford J.; Torriani, Martin; Miller, Karen K.

    2014-01-01

    Purpose Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. Materials and Methods In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21–45y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. Results GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. Six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. Six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor

  19. Organizational Career Growth, Affective Occupational Commitment and Turnover Intentions

    ERIC Educational Resources Information Center

    Weng, Qingxiong; McElroy, James C.

    2012-01-01

    Survey data, collected from the People's Republic of China, were used to test Weng's (2010) four facet model of career growth and to examine its effect on occupational commitment and turnover intentions. Weng conceptualized career growth as consisting of four factors: career goal progress, professional ability development, promotion speed, and…

  20. Factors Affecting Principal Turnover: A Study of Three Midwestern Cities

    ERIC Educational Resources Information Center

    Belt, Charles M.

    2009-01-01

    Purpose. This dissertation addresses the problem of principal turnover. Using state and city level administrative data, a study of principals and their schools in greater Kansas City, Missouri, St. Louis, Missouri, and Milwaukee, Wisconsin, was conducted with the goal of discovering themes that emerge regarding the factors associated with turnover…

  1. Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects.

    PubMed

    Tjhia, Crystal K; Stover, Susan M; Rao, D Sudhaker; Odvina, Clarita V; Fyhrie, David P

    2012-07-01

    Mineralization of bone, from the tissue level to whole bones, is associated with mechanical properties. The relationship between bone tissue mineralization and micromechanical properties may be affected by age, disease, and drug treatment. Patients with severely suppressed bone turnover (SSBT) suffered atypical fractures while on bisphosphonate treatment. The role of tissue level mineralization in predicting material level properties of SSBT bone may be different from that of other osteoporotic patients and of normal subjects. The aim of this study was to compare the relationships between mineralization and micromechanical properties of bone biopsies from patients with SSBT, bisphosphonate-naive osteoporotic patients with typical vertebral fracture, and normal young and age-matched subjects. We used nanoindentation and quantitative backscattered electron microscopy to characterize the elastic modulus, contact hardness, plastic deformation resistance, and tissue mineralization of the biopsies at site-matched locations within each biopsy. The linear mineralization-mechanical property relationships were different among the groups with respect to the intercepts for only cortical bone tissue but not the slopes for cortical and trabecular bone tissues. For a given mineral density, there was a trend of greater plastic deformation resistance in SSBT cortical bone compared to young normal bone. Similarly, there was a trend of greater plastic deformation resistance in osteoporotic trabecular bone compared to young normal bone for a given mineral density. The age-matched normal group had higher elastic modulus and a trend of higher contact hardness compared to the young normal group for a given mineral density. However, the mechanical property-mineralization relationships within an individual were weak, and only 21 of 53 biopsies that were analyzed had at least one significant association between mineralization and a mechanical property measurement for either cortical or

  2. Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats.

    PubMed

    Nebot, E; Aparicio, V A; Camiletti-Moirón, D; Martinez, R; Erben, R G; Kapravelou, G; Sánchez-González, C; De Teresa, C; Porres, J M; López-Jurado, M; Aranda, P; Pietschmann, P

    2016-06-01

    Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality. PMID:26801156

  3. Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report.

    PubMed

    Kodama, Yasumitsu; Ogose, Akira; Oguri, Yoshimitsu; Ubaidus, Sobhan; Iizuka, Tateyuki; Takagi, Ritsuo

    2012-09-01

    A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

  4. The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women

    PubMed Central

    Shin, Chaeho; Lee, Seung Hun; Koh, Jung-Min

    2016-01-01

    Background Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women. Methods A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria. Results Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73). Conclusion This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women. PMID:27469066

  5. Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice.

    PubMed

    Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

    2016-10-01

    The third generation aromatase inhibitors are currently the drugs of choice for the treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In this study, we compared the effects of a nonsteroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa B ligand (RANKL), sclerostin, and dickkopf-1 (DKK-1) in vinylcyclohexene diepoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1 mg/kg) administration for 1 month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice. Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone. PMID:27279630

  6. Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice.

    PubMed

    Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

    2016-10-01

    The third generation aromatase inhibitors are currently the drugs of choice for the treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In this study, we compared the effects of a nonsteroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa B ligand (RANKL), sclerostin, and dickkopf-1 (DKK-1) in vinylcyclohexene diepoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1 mg/kg) administration for 1 month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice. Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone.

  7. The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.

    PubMed

    Cavalier, E; Bergmann, P; Bruyère, O; Delanaye, P; Durnez, A; Devogelaer, J-P; Ferrari, S L; Gielen, E; Goemaere, S; Kaufman, J-M; Toukap, A Nzeusseu; Reginster, J-Y; Rousseau, A-F; Rozenberg, S; Scheen, A J; Body, J-J

    2016-07-01

    The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis. PMID:27026330

  8. Piribedil affects dopamine turnover in cochleas stimulated by white noise.

    PubMed

    Gil-Loyzaga, P; Vicente-Torres, M A; Fernández-Mateos, P; Arce, A; Esquifino, A

    1994-09-01

    The presence of dopamine (DA) within the cochlea has been previously reported, indicating that its turnover increases under noise stimulation. In the present report, piribedil, a dopaminergic D2 agonist, was used in order to provide evidence of the activity of D2 receptors in the turnover of DA under noise stimulation. Long-Evans rats were intraperitoneally injected with distilled water or with a solution of piribedil one hour previously to either noise or silence exposure. Noise stimulation was performed in an anechoic chamber at 70, 90 or 110 dB SPL for one hour. The animals were then sacrificed and the cochlear contents of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were quantified by HPLC with electrochemical detection. The administration of piribedil to animals kept in silence did not modify the cochlear DA, DOPAC and HVA content. Noise stimulation resulted in a decrease of the cochlear DA content and an increase of the cochlear DOPAC and HVA contents in vehicle treated animals. The administration of piribedil resulted in a blockade of this noise induced cochlear DA turnover. These results suggest that piribedil stimulates cochlear D2 receptors controlling the cochlear DA release. Piribedil action on D2 receptors could explain the improvement observed in some cochleo-vestibular diseases signs after piribedil treatment. PMID:7806480

  9. The regulation of bone turnover in ameloblastoma using an organotypic in vitro co-culture model

    PubMed Central

    Eriksson, Tuula M; Day, Richard M; Fedele, Stefano; Salih, Vehid M

    2016-01-01

    Ameloblastoma is a rare, odontogenic neoplasm with benign histopathology, but extensive, local infiltrative capacity through the bone tissue it originates in. While the mechanisms of ameloblastoma invasion through the bone and bone absorption are largely unknown, recent investigations have indicated a role of the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand regulatory mechanisms. Here, we present results obtained using a novel in vitro organotypic tumour model, which we have developed using tissue engineering techniques. Using this model, we analysed the expression of genes involved in bone turnover and detected a 700-fold increase in receptor activator of nuclear factor kappa-B ligand levels in the co-culture models with ameloblastoma cells cultured with bone cells. The model described here can be used for gene expression studies, as a basis for drug testing or for a more tailored platform for testing of the behaviour of different ameloblastoma tumours in vitro. PMID:27746893

  10. Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis: a literature review.

    PubMed

    Coiffier, Guillaume; Bouvard, Béatrice; Chopin, Florance; Biver, Emmanuel; Funck-Brentano, Thomas; Garnero, Patrick; Guggenbuhl, Pascal

    2013-05-01

    We studied the impact of inflammatory rheumatism and its treatment on the most common bone turnover markers, based on six previously defined questions in a systematic literature review in order to define their place in daily clinical practice. The role of bone is currently considered of particular importance concerning cartilage damage in inflammatory rheumatism (rheumatoid arthritis and ankylosing spondylitis) and the new concept of osteoimmunology has emerged. Some bone turnover markers are available in clinical practice. In spite of rich and extensive literature on bone turnover markers, their use in inflammatory rheumatism or even osteoporosis is not clear, and a systematic literature review became necessary. In spite of a large number of different markers used in literature, few of them that are useful in common practice have been studied in the field of inflammatory rheumatism such as rheumatoid arthritis and ankylosing spondylitis. Although their study enables understanding of the physiopathological mechanisms of osteoporosis in inflammatory rheumatism, their use in current common practice cannot be recommended. Interesting data on the forecast of the structural evolution of rheumatoid arthritis has been found within the framework of clinical research, without any real practical impact today.

  11. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications. PMID:27049105

  12. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

  13. Changes in Bone Turnover Markers and Bone Mass with Reducing Levels of Jumping Exercise Regimens in Female Rats

    PubMed Central

    Ooi, Foong Kiew; Singh, Rabindarjeet; Singh, Harbindar Jeet

    2012-01-01

    Purpose To date, little is known about the effects of a reduced level of jumping exercise regimens on bone turnover markers and mass. This study investigates the effects of different jumping exercise regimens with varying exercise loads on serum bone turnover markers and bone mass in female rats. Methods A total of 144 female rats aged 12 weeks, were divided into 12 groups as follows: no exercise for 8 (8S) or 32 weeks (32S), or 8 weeks of standard training program (8STP) consisting of 200 jumps per week (200J/w), given at 40 jumps per day (40J/d) for 5 days per week (5d/w) (8STP24E), followed by 24 weeks of exercise at loads of either 10J/d or 20J/d or 40J/d, for either 5d/w, or 3d/w, or 1d/w. Serum osteocalcin, alkaline phosphatase, C-terminal telopeptide of type 1 collagen (1CTP) concentrations, and tibial fat free dry weight were measured. Results Tibial mass was significantly higher in 8STP than 8S. No changes were evident in serum markers of bone turnover parameters after 8STP. Significant increases in tibial mass were observed in rats that continued to exercise at workloads of 30J/w and above after 8STP. Serum alkaline phosphatase concentrations increase whereas serum 1CTP concentrations decrease in rats given workloads of 40J/w and above. Conclusions It appears, an exercise load of 30J/w, i.e. 10J/d for 3d/w, was the minimum level of continuous exercise load that was required to maintain the 8STP-induced bone gains. In addition, significant increases in bone mass in young rats following 8STP might not always be reflected by changes in serum levels of osteocalcin, alkaline phosphatase and 1CTP. PMID:23342220

  14. Associations of total, dairy, and meat protein with markers for bone turnover in healthy, prepubertal boys.

    PubMed

    Budek, Alicja Z; Hoppe, Camilla; Michaelsen, Kim F; Bügel, Susanne; Mølgaard, Christian

    2007-04-01

    We previously reported that high intake of milk, but not meat, equal in protein content, increased serum insulin-like growth factor-I (sIGF-I) in prepubertal boys. sIGF-I plays a key role in bone metabolism. Therefore, the aim of this cross-sectional study was to investigate associations of total, dairy, and meat protein intake with markers for bone turnover and sIGF-I in prepubertal, healthy boys (n = 81). We measured bone turnover (enzyme-linked immunoassay) in serum osteocalcin (sOC), bone-specific alkaline phosphatase (sBAP), and C-terminal telopeptide of collagen type-I (sCTX); dietary intake was estimated from a 3-d weighed food record. sIGF-I and its binding protein-3 were assessed (immunoassay) in a subgroup of 56 boys. All statistical models included effects of age, BMI, and energy intake. Dairy protein was negatively associated with sOC (P = 0.05) but not significantly associated with sBAP and sCTX. Further analyses showed that dairy protein decreased (P = 0.05) sOC at a high meat protein intake (>0.8 g/kg), whereas meat protein increased (P = 0.03) sOC at a low dairy protein intake (<0.4 g/kg). Total and meat protein intake was positively associated with sBAP (P < or = 0.04) but not significantly associated with sOC and sCTX. Free sIGF-I was positively associated with total (P < 0.01) and dairy (P = 0.06) protein but not with meat protein. Our results indicate that dairy and meat protein may exhibit a distinct regulatory effect on different markers for bone turnover. Future studies should focus on differential effects of dairy and meat protein on bone health during growth.

  15. Ankle-brachial index and bone turnover in patients on dialysis.

    PubMed

    London, Gérard M; Marchais, Sylvain J; Guérin, Alain P; de Vernejoul, Marie-Christine

    2015-02-01

    An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.

  16. Ankle-Brachial Index and Bone Turnover in Patients on Dialysis

    PubMed Central

    Marchais, Sylvain J.; Guérin, Alain P.; de Vernejoul, Marie-Christine

    2015-01-01

    An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH. PMID:25231881

  17. Biochemical markers of bone' turnover in cosmonauts after long term space flight

    NASA Astrophysics Data System (ADS)

    Larina, I. M.; Morukov, B. V.; Tret'yakov, V. S.

    There were investigated biochemical markers of bone tissue' turnover by mean determination of osteocalcin (as parameter of bone construction de novo) and crosslinks (as parameters of bone' collagen destruction). The mineral-tropic hormones -- parathyroid hormone, calcitonine -- and ionized calcium have been determined as well in blood of cosmonauts who carried out long term space flights on Russian module of ISS in 2000-2003. Samples of blood were collected from 9 cosmonauts whose flight duration was between 4 and 6 months. The level of total calcium in blood was unchanged in landing day, comparing with pre-flight concentration, but the activity of ionized calcium was elevated during first recovery week (1,18± 0,02 vs 1,26± 0,03 mmol/L; p<0,05). In the same period of time the concentration on PTH was stable and higher then before launch (171± 52 & 172± 39, %% to pre-flight) and CT level continued to grow (from 190± 77 to 235± 83, %% to pre-flight). Additionally it was shown that post-flight concentration of both bone turnover markers in blood of participants of space missions has been higher than before flight. So after flight, relatively to preflight period, the elevation of both processes' activity was happened: the bone' destruction and bone construction de novo as well. Nevertheless post-flight dynamics of these processes was different - the marker of bone collagen destruction was decreased from the 1st to 14th days of recovery period (181,84% & 149,47%, relatively) and the marker of bone construction de novo was lightly increased (110,7% & 125,1%). We concede that during post-flight period calcium homeostasis was supported by tension of hormonal regulation. It can be noted that within the bone metabolism of calcium the process of osteosynthesis looks to be activated in this period but osteolisis is still remained. In this case the re-establishment of normal bone calcium turnover will occur later.

  18. Disruption of c-Kit Signaling in Kit(W-sh/W-sh) Growing Mice Increases Bone Turnover.

    PubMed

    Lotinun, Sutada; Krishnamra, Nateetip

    2016-01-01

    c-Kit tyrosine kinase receptor has been identified as a regulator of bone homeostasis. The c-Kit loss-of-function mutations in WBB6F1/J-Kit(W/W-v) mice result in low bone mass. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to a sex hormone deficiency. In contrast, C57BL/6J-Kit(W-sh)/(W-sh) (W(sh)/W(sh)) mice, which carry an inversion mutation affecting the transcriptional regulatory elements of the c-Kit gene, are fertile. Here, we showed that W(sh)/W(sh) mice exhibited osteopenia with elevated bone resorption and bone formation at 6- and 9-week-old. The c-Kit W(sh) mutation increased osteoclast differentiation, the number of committed osteoprogenitors, alkaline phosphatase activity and mineralization. c-Kit was expressed in both osteoclasts and osteoblasts, and c-Kit expression was decreased in W(sh)/W(sh)osteoclasts, but not osteoblasts, suggesting an indirect effect of c-Kit on bone formation. Furthermore, the osteoclast-derived coupling factor Wnt10b mRNA was increased in W(sh)/W(sh) osteoclasts. Conditioned medium from W(sh)/W(sh) osteoclasts had elevated Wnt10b protein levels and induced increased alkaline phosphatase activity and mineralization in osteoblast cultures. Antagonizing Wnt10b signaling with DKK1 or Wnt10b antibody inhibited these effects. Our data suggest that c-Kit negatively regulates bone turnover, and disrupted c-Kit signaling couples increased bone resorption with bone formation through osteoclast-derived Wnt 10 b. PMID:27527615

  19. Disruption of c-Kit Signaling in KitW-sh/W-sh Growing Mice Increases Bone Turnover

    PubMed Central

    Lotinun, Sutada; Krishnamra, Nateetip

    2016-01-01

    c-Kit tyrosine kinase receptor has been identified as a regulator of bone homeostasis. The c-Kit loss-of-function mutations in WBB6F1/J-KitW/W-v mice result in low bone mass. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to a sex hormone deficiency. In contrast, C57BL/6J-KitW-sh/W-sh (Wsh/Wsh) mice, which carry an inversion mutation affecting the transcriptional regulatory elements of the c-Kit gene, are fertile. Here, we showed that Wsh/Wsh mice exhibited osteopenia with elevated bone resorption and bone formation at 6- and 9-week-old. The c-Kit Wsh mutation increased osteoclast differentiation, the number of committed osteoprogenitors, alkaline phosphatase activity and mineralization. c-Kit was expressed in both osteoclasts and osteoblasts, and c-Kit expression was decreased in Wsh/Wshosteoclasts, but not osteoblasts, suggesting an indirect effect of c-Kit on bone formation. Furthermore, the osteoclast-derived coupling factor Wnt10b mRNA was increased in Wsh/Wsh osteoclasts. Conditioned medium from Wsh/Wsh osteoclasts had elevated Wnt10b protein levels and induced increased alkaline phosphatase activity and mineralization in osteoblast cultures. Antagonizing Wnt10b signaling with DKK1 or Wnt10b antibody inhibited these effects. Our data suggest that c-Kit negatively regulates bone turnover, and disrupted c-Kit signaling couples increased bone resorption with bone formation through osteoclast-derived Wnt 10 b. PMID:27527615

  20. Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

    PubMed

    Oesterreich, Steffi; Henry, N Lynn; Kidwell, Kelley M; Van Poznak, Catherine H; Skaar, Todd C; Dantzer, Jessica; Li, Lang; Hangartner, Thomas N; Peacock, Munro; Nguyen, Anne T; Rae, James M; Desta, Zeruesenay; Philips, Santosh; Storniolo, Anna M; Stearns, Vered; Hayes, Daniel F; Flockhart, David A

    2015-11-01

    Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway. PMID:26536870

  1. Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population.

    PubMed

    Dai, Zhaoli; Wang, Renwei; Ang, Li-Wei; Yuan, Jian-Min; Koh, Woon-Puay

    2016-02-01

    While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case-control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45-74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p<0.05). There was a dose-dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend≤0.006), where the risk was significantly increased by 4.32-8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02-21.18) for PINP and 4.92 (1.67-14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53-21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3-Q4) to those with low levels of PINP (Q1-Q3) and CTX-I (Q1-Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population.

  2. The pitfall of treating low bone turnover: Effects on cortical porosity.

    PubMed

    Araujo, Maria Julia C L N; Karohl, Cristina; Elias, Rosilene M; Barreto, Fellype C; Barreto, Daniela Veit; Canziani, Maria Eugenia F; Carvalho, Aluizio B; Jorgetti, Vanda; Moyses, Rosa M A

    2016-10-01

    Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

  3. Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis.

    PubMed

    Wisłowska, Margaret; Jakubicz, Danuta; Stepień, Krystyna; Cicha, Małgorzata

    2009-10-01

    Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at

  4. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  5. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    PubMed

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  6. Kinetic measurements of bone mineral metabolism: The use of Na-22 as a tracer for long-term bone mineral turnover studies

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1978-01-01

    Sodium-22 was studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with (22)Na which is released through the metabolic turnover of the bone. The (22)Na which is not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high but nontoxic levels of NaCl. The (22)Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  7. Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

    PubMed

    Bristow, Sarah M; Gamble, Greg D; Stewart, Angela; Horne, Lauren; House, Meaghan E; Aati, Opetaia; Mihov, Borislav; Horne, Anne M; Reid, Ian R

    2014-11-28

    Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

  8. Physical activity and bone turnover markers: a cross-sectional and a longitudinal study.

    PubMed

    Adami, Silvano; Gatti, Davide; Viapiana, Ombretta; Fiore, Carmelo Erio; Nuti, Ranuccio; Luisetto, Giovanni; Ponte, Marco; Rossini, Maurizio

    2008-12-01

    Strenuous physical activity in young individuals has an important effect on both bone mass and bone turnover but the effect of moderate physical activity in adults remains uncertain. In a large cohort (N = 530) of healthy premenopausal women, bone formation markers (osteocalcin and N-terminal propeptide of type 1 procollagen [P1NP]), but not serum C-telopeptide of type 1 collagen (sCTX), were found to be significantly associated with the level of physical activity, and this association remained significant after adjusting the data (ANCOVA) by age and body mass index. Mean spine and hip bone mineral density (BMD) values were positively associated with physical activity but this was statistically significant (P = 0.050) only for adjusted values of spine BMD. Twenty-four healthy sedentary premenopausal women, subscribing to participate in a community exercise program lasting a month, and 18 age-matched controls were included in the longitudinal study. Serum osteocalcin and P1NP, but not sCTX, rose significantly, by ca. 25%, only in the active group after a month of exercise. The changes in the two bone formation markers remained statistically significant for values adjusted for body weight, which fell significantly in the exercise group. In conclusion, both the cross-sectional and the longitudinal parts of our study demonstrate that even minor changes in physical activity are associated with a clear effect on bone formation markers.

  9. Effects of endocrine and inflammatory changes on markers of bone turnover following Roux-en-Y gastric bypass surgery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bariatric surgery is associated with increased bone turnover. The mechanisms involved are unclear but may involve nutrition, mechanical unloading, altered secretion of gastrointestinal and adipose hormones and changes in inflammatory status leading to weight loss induced bone loss. We assessed marke...

  10. Changes of mesenchymal stromal cells mobilization and bone turnover in an experimental bone fracture model in ovariectomized mice

    PubMed Central

    Pang, Jian; Guo, Hai-Ling; Ding, Dao-Fang; Wu, Yu-Yun; Zhao, Yong-Fang; Gu, Xin-Feng; Zheng, Yu-Xin

    2015-01-01

    Objective: The aim of this study was to characterize the mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) mobilization, and bone turnover in osteoporotic fracture healing in ovariectomized mice. Methods: In total, 112 female C57/BL mice were divided into two groups. The first group was sham-operated (SO), and the other group was ovariectomized (OVX). After three weeks, the right femora of the mice were fractured under anesthesia and internally fixed with steel pin. Peripheral blood and bone marrow were was collected for flow cytometry analysis, at 0 hours (h), 12 h, 24 h, 72 h and 168 h after fracture. MSCs and EPCs levels were assessed using cell surface antigens in different combinations (CD44+ CD34-CD45-, and CD34+ KDR+CD45-) by flow cytometry. At 0, 14, 28 and 42 days after fracture, sera were assayed for circulating levels of procollagen type I-N-terminal propeptide (P1NP) and C-terminal telopeptide of type I-collagen (CTX) by ELISA. Femurs were harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT) and histology. Results: Our results showed that bone marrow and peripheral blood MSCs numbers of the OVX mice were significantly lower than the SO mice, at 12 h, 24 h and 72 h after fracture. In addition, circulating P1NP and CTX levels of the OVX mice were significantly higher than the SO mice, at 2 and 4 weeks. Conclusion: Results of the present study revealed disorders of bone marrow MSCs mobilization and bone turnover may partially account for the delay of osteoporotic fracture healing. PMID:26617731

  11. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

    PubMed Central

    Salerni, H.; González, D.; Bagur, A.; Oliveri, B.; Farías, V.; Maffei, L.; Mansur, J. L.; Larroudé, M. S.; Pavlove, M. M.; Karlsbrum, S.

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. PMID:27579211

  12. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

    PubMed

    Sánchez, A; Brun, L R; Salerni, H; Costanzo, P R; González, D; Bagur, A; Oliveri, B; Zanchetta, M B; Farías, V; Maffei, L; Premrou, V; Mansur, J L; Larroudé, M S; Sarli, M A; Rey, P; Ulla, M R; Pavlove, M M; Karlsbrum, S; Brance, M L

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. PMID:27579211

  13. Combined effects of positive and negative affectivity and job satisfaction on job performance and turnover intentions.

    PubMed

    Bouckenooghe, Dave; Raja, Usman; Butt, Arif Nazir

    2013-01-01

    Capturing data from employee-supervisor dyads (N = 321) from eight organizations in Pakistan, including human service organizations, an electronics assembly plant, a packaging material manufacturing company, and a small food processing plant, we used moderated regression analysis to examine whether the relationships between trait affect (positive affectivity [PA] and negative affectivity [NA]) and two key work outcome variables (job performance and turnover) are contingent upon the level of job satisfaction. We applied the Trait Activation Theory to explain the moderating effect of job satisfaction on the relationship between affect and performance and between affect and turnover. Overall, the data supported our hypotheses. Positive and negative affectivity influenced performance and the intention to quit, and job satisfaction moderated these relationships. We discuss in detail the results of these findings and their implications for research and practice.

  14. Combined effects of positive and negative affectivity and job satisfaction on job performance and turnover intentions.

    PubMed

    Bouckenooghe, Dave; Raja, Usman; Butt, Arif Nazir

    2013-01-01

    Capturing data from employee-supervisor dyads (N = 321) from eight organizations in Pakistan, including human service organizations, an electronics assembly plant, a packaging material manufacturing company, and a small food processing plant, we used moderated regression analysis to examine whether the relationships between trait affect (positive affectivity [PA] and negative affectivity [NA]) and two key work outcome variables (job performance and turnover) are contingent upon the level of job satisfaction. We applied the Trait Activation Theory to explain the moderating effect of job satisfaction on the relationship between affect and performance and between affect and turnover. Overall, the data supported our hypotheses. Positive and negative affectivity influenced performance and the intention to quit, and job satisfaction moderated these relationships. We discuss in detail the results of these findings and their implications for research and practice. PMID:23469474

  15. Dietary protein level and source differentially affect bone metabolism, strength, and intestinal calcium transporter expression during ad libitum and food-restricted conditions in male rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High protein diets may attenuate bone loss during energy restriction (ER). The objective of the current study was to determine whether high protein diets suppress bone turnover and improve bone quality in rats during ER and whether dietary protein source affects this relationship. Eighty 12-week o...

  16. Strategies to affect bone remodeling: osteointegration.

    PubMed

    LeGeros, R Z; Craig, R G

    1993-12-01

    Osteointegration was defined as a "direct structural and functional connection between ordered living bone and the surface of a load-carrying implant." Although osteointegration was meant originally to describe a biologic fixation of the titanium dental implants, it is now used to describe the attachment of other materials used for dental and orthopedic applications as well. Analyses of material-bone interface showed that osteointegrated implants can have an intervening fibrous layer or direct bone apposition characterized by bone-bonding depending on the composition and surface properties of the biomaterial. This article reviews biologic (host tissue properties and response), biomechanical, and biomaterial factors affecting osteointegration. Biologic factors include the quality of bone. Biomaterial factors include the effect of material composition on the bone-material interface. Suggested areas for future research include determining the correlation between oral bone status and osteoporosis, the effect of gender, age, and endocrine status (e.g., osteoporosis) on implant success or failure, the effect of calcium phosphate coating composition and crystallinity on in vivo performance of implants, the factors contributing to accelerated osteointegration, and development of osteoinductive implants.

  17. Biochemical Markers of Bone Turnover in Percutaneous Vertebroplasty for Osteoporotic Compression Fracture

    SciTech Connect

    Komemushi, Atsushi Tanigawa, Noboru; Kariya, Shuji; Kojima, Hiroyuki; Shomura, Yuzo; Tokuda, Takanori; Nomura, Motoo; Terada, Jiro; Kamata, Minoru; Sawada, Satoshi

    2008-03-15

    Purpose. To evaluate relationships between biochemical markers of bone turnover, bone mineral density, and new compression fractures following vertebroplasty. Methods. Initially, we enrolled 30 consecutive patients with vertebral compression fractures caused by osteoporosis. Twenty-three of the 30 patients visited our hospital for follow-up examinations for more than 4 weeks after vertebroplasty. The patients were divided into two groups: patients with new fractures (group F) and patients with no new fractures (group N). We analyzed differences in the following parameters between these two groups: serum bone alkaline phosphatase, urinary crosslinked N-telopeptide of type I collagen, urinary deoxypyridinoline, and bone mineral density. Next, the patients were divided into another two groups: patients with higher risk (group H: urinary crosslinked N-telopeptide of type I collagen >54.3 nmol BCE/mmol Cr or urinary deoxypyridinoline >7.6 nmol/mmol Cr, and serum bone alkaline phosphatase <29.0 U/l) and patients with lower risk (group L). We analyzed the difference in the rate of new fractures between these two groups. Results. We identified 9 new fractures in 7 patients. There were no significant differences between groups F and N. We identified 5 new fractures in 3 of the 4 patients in group H, and 4 new fractures in 4 of the 19 patients in group L. There was a significant difference in the rate of new fractures between groups H and L. Conclusions. A combination of high levels of bone resorption markers and normal levels of bone formation markers may be associated with increased risk of new recurrent fractures after percutaneous vertebroplasty.

  18. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    SciTech Connect

    Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  19. Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature.

    PubMed

    Sousa, Cristina P; Dias, Isabel R; Lopez-Peña, Mónica; Camassa, José A; Lourenço, Paulo J; Judas, Fernando M; Gomes, Manuela E; Reis, Rui L

    2015-01-01

    Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome. PMID:25993365

  20. Bone turnover markers in patients with prostate carcinoma: influence of sex steroids levels.

    PubMed

    Varsavsky, Mariela; Reyes-García, Rebeca; García-Martín, Antonia; Rozas-Moreno, Pedro; González-Ramírez, Rocío; Rocío, González-Ramírez; Muñoz-Torres, Manuel

    2014-01-01

    There are limited data about bone turnover markers (BTM) in androgen deprivation therapy (ADT)-treated prostate cancer (PCa) patients, and the relationship between sex steroids, bone mass, and BTM has not been explored. Our objective was to analyze the influence of sex steroids levels on BTM in patients with PCa treated with or without ADT. We performed a cross-sectional study including 83 subjects with PCa (54% with ADT). BTM, bone mineral density (BMD), and sex steroids were determined. BTM were inversely related to serum level of estrogens. Tartrate-specific acid phosphatase (TRAP-5b) showed a negative correlation with free estradiol (Free E) (r = -0.274, p = 0.014) and Bio E (r = -0.256, p = 0.022) that remained after adjustment for age: Free E (β = -0.241, p = 0.03) and Bio E (β = -0.213, p = 0.063). Bone-specific alkaline phosphatase (BSAP) concentrations were inversely related to Free E (r = -0.281, p = 0.011, age-adjusted β = -0.256, p = 0.024). There was a negative correlation between osteocalcin (OC) levels and Free E (r = -0.195, p = 0.082; age-adjusted β = -0.203, p = 0.076) and Bio E (r = -0.215, p = 0.054; age-adjusted β = -0.240, p = 0.039). BTM and androgens were inversely related to TRAP-5b: total testosterone (total T) (r = -0.238, p = 0.033), Free T (r = -0.309, p = 0.05), and Bio T (r = -0.310, p = 0.05), but these correlations disappeared after age-adjustment. We did not find any relationship between BMD at different locations and sex steroids. In conclusion, in patients with PCa, estrogen levels influence bone resorption and bone formation whereas androgens may exert actions only in bone resorption. These results suggest that estradiol is the main sex steroid that regulates bone metabolism in males with prostate carcinoma.

  1. Weight-bearing exercise and markers of bone turnover in female athletes.

    PubMed

    Creighton, D L; Morgan, A L; Boardley, D; Brolinson, P G

    2001-02-01

    Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers. PMID:11160054

  2. Weight-bearing exercise and markers of bone turnover in female athletes.

    PubMed

    Creighton, D L; Morgan, A L; Boardley, D; Brolinson, P G

    2001-02-01

    Weight-bearing activity provides an osteogenic stimulus, while effects of swimming on bone are unclear. We evaluated bone mineral density (BMD) and markers of bone turnover in female athletes (n = 41, age 20.7 yr) comparing three impact groups, high impact (High, basketball and volleyball, n = 14), medium impact (Med, soccer and track, n = 13), and nonimpact (Non, swimming, n = 7), with sedentary age-matched controls (Con, n = 7). BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck (FN), Ward's triangle, and trochanter (TR); bone resorption estimated from urinary cross-linked N-telopeptides (NTx); and bone formation determined from serum osteocalcin. Adjusted BMD (g/cm; covariates: body mass index, weight, and calcium and calorie intake) was greater at the FN and TR in the High group (1.27 +/- 0.03 and 1.05 +/- 0.03) than in the Non (1.05 +/- 0.04 and 0.86 +/- 0.04) and Con (1.03 +/- 0.05 and 0.85 +/- 0.05) groups and greater at the TR in the Med group (1.01 +/- 0.03) than in the Non (0.86 +/- 0.04) and Con (0.85 +/- 0.05) groups. Total body BMD was higher in the High group (4.9 +/- 0.12) than in the Med (4.5 +/- 0.12), Non (4.2 +/- 0.14), and Con (4.1 +/- 0.17) groups and greater in the Med group than in the Non and Con groups. Bone formation was lower in the Non group (19.8 +/- 2.6) than in the High (30.6 +/- 3.0) and Med (32.9 +/- 1.9, P < or = 0.05) groups. No differences in a marker of bone resorption (NTx) were noted. This indicates that women who participate in impact sports such as volleyball and basketball had higher BMDs and bone formation values than female swimmers.

  3. Bone Turnover in Wild Type and Pleiotrophin-Transgenic Mice Housed for Three Months in the International Space Station (ISS)

    PubMed Central

    Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

    2012-01-01

    Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity’s negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice. PMID:22438896

  4. How Does Supervisor Support Influence Turnover Intent Among Frontline Hospital Workers? The Mediating Role of Affective Commitment.

    PubMed

    Nichols, Helen M; Swanberg, Jennifer E; Bright, Charlotte Lyn

    2016-01-01

    Turnover among frontline hospital service workers can disrupt organizational effectiveness, reduce profitability, and limit the ability to provide high-quality, patient-centered care. This concern is compounded by the increasing reliance on frontline supervisors to manage this workforce, often without necessary training and support. However, research addressing the relationship between frontline supervisor support and intent to turnover among service workers and the process by which these variables are related is limited. By surveying 270 housekeeping and dietary service workers employed at 2 US hospitals, this study examined the relationship between supervisor support and turnover intent and assessed the mediating role of affective commitment between supervisor support and intent to turnover. Turnover intentions were lower for workers who reported greater levels of supervisor support and affective commitment; both supervisor support and affective commitment were significant predictors of turnover intent when tested individually. However, when controlling for affective commitment, supervisor support no longer predicted turnover intent, indicating that affective commitment fully mediated the relationship between supervisor support and intent to turnover. Implications for further research and organizational practice are discussed. PMID:27455369

  5. How Does Supervisor Support Influence Turnover Intent Among Frontline Hospital Workers? The Mediating Role of Affective Commitment.

    PubMed

    Nichols, Helen M; Swanberg, Jennifer E; Bright, Charlotte Lyn

    2016-01-01

    Turnover among frontline hospital service workers can disrupt organizational effectiveness, reduce profitability, and limit the ability to provide high-quality, patient-centered care. This concern is compounded by the increasing reliance on frontline supervisors to manage this workforce, often without necessary training and support. However, research addressing the relationship between frontline supervisor support and intent to turnover among service workers and the process by which these variables are related is limited. By surveying 270 housekeeping and dietary service workers employed at 2 US hospitals, this study examined the relationship between supervisor support and turnover intent and assessed the mediating role of affective commitment between supervisor support and intent to turnover. Turnover intentions were lower for workers who reported greater levels of supervisor support and affective commitment; both supervisor support and affective commitment were significant predictors of turnover intent when tested individually. However, when controlling for affective commitment, supervisor support no longer predicted turnover intent, indicating that affective commitment fully mediated the relationship between supervisor support and intent to turnover. Implications for further research and organizational practice are discussed.

  6. Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the r...

  7. Flaxseed enhances the beneficial effect of low-dose estrogen therapy at reducing bone turnover and preserving bone microarchitecture in ovariectomized rats.

    PubMed

    Sacco, Sandra M; Chen, Jianmin; Ganss, Bernhard; Thompson, Lilian U; Ward, Wendy E

    2014-07-01

    Our previous research showed greatest protection to vertebral bone mineral density and strength in ovariectomized (OVX) rats when lignan- and α-linolenic acid-rich flaxseed (FS) is combined with low-dose estrogen therapy (LD) compared with either treatment alone. This study determined the effects of combined FS+LD on serum and tissue markers of bone turnover and microarchitecture to explain our previous findings. Three-month-old OVX rats were randomized to negative control (NEG), FS, LD or FS+LD for 2 or 12 weeks, meaningful time points for determining effects on markers of bone metabolism and bone structure, respectively. Ground FS was added to the AIN-93M diet (100 g/kg diet) and LD (0.42 μg 17β-estradiol/(kg body weight·day)) was delivered by subcutaneous implant. Sham rats were included as positive control. Bone formation (e.g., osteocalcin), bone resorption (e.g., tartrate-resistant acid phosphatase-5β (TRAP-5β)), as well as osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANKL) were analyzed from the 2-week study by commercial assays (serum) and (or) histology (vertebra). Vertebral bone microarchitecture was measured from the 12-week study using microcomputed tomography. In serum, FS+LD and LD induced lower TRAP-5β and osteocalcin, and higher OPG and OPG/RANKL ratio versus NEG and FS (p < 0.05). In vertebrae, FS+LD induced higher OPG and lower osteocalcin versus NEG (p < 0.01) and did not differ from LD and FS. FS+LD improved bone microarchitecture versus NEG, FS, and LD (p < 0.05). In conclusion, FS+LD protects bone tissue because of a reduction in bone turnover. However, elucidating the distinctive action of FS+LD on bone turnover compared with LD requires further investigation.

  8. Increased Intake of Selected Vegetables, Herbs and Fruit may Reduce Bone Turnover in Post-Menopausal Women

    PubMed Central

    Gunn, Caroline Ann; Weber, Janet Louise; McGill, Anne-Thea; Kruger, Marlena Cathorina

    2015-01-01

    Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation. PMID:25856221

  9. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

    PubMed

    Hoy, Jennifer; Grund, Birgit; Roediger, Mollie; Ensrud, Kristine E; Brar, Indira; Colebunders, Robert; Castro, Nathalie De; Johnson, Margaret; Sharma, Anjali; Carr, Andrew

    2013-06-01

    Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ≤ 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.

  10. Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover

    PubMed Central

    Wilson, Caroline; Gossiel, Fatma; Leonard, Robert; Anderson, Richard A; Adamson, Douglas J A; Thomas, Geraldine; Coleman, Robert E

    2016-01-01

    Background The Ovarian Protection Trial In Premenopausal Breast Cancer Patients “OPTION” trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6–8 cycles of (neo)adjuvant chemotherapy (CT) +/− goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover. Methods Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (≤40 vs >40 years) and with exploratory analysis according to POI rates at 12 months. Results In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. Conclusion Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI. PMID:26998426

  11. Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

    PubMed

    Ahmad, A M; Hopkins, M T; Fraser, W D; Ooi, C G; Durham, B H; Vora, J P

    2003-02-01

    Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0

  12. Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition.

    PubMed

    Crandall, Carolyn J; Tseng, Chi-Hong; Crawford, Sybil L; Thurston, Rebecca C; Gold, Ellen B; Johnston, Janet M; Greendale, Gail A

    2011-04-01

    The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health.

  13. Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

    PubMed

    Ok, Ercan; Asci, Gulay; Bayraktaroglu, Selen; Toz, Huseyin; Ozkahya, Mehmet; Yilmaz, Mumtaz; Kircelli, Fatih; Sevinc Ok, Ebru; Ceylan, Naim; Duman, Soner; Cirit, Mustafa; Monier-Faugere, Marie-Claude; Malluche, Hartmut H

    2016-08-01

    Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

  14. The Factors Affecting Bone Density in Cirrhosis

    PubMed Central

    Hajiabbasi, Asghar; Shafaghi, Afshin; Fayazi, Haniyeh Sadat; Shenavar Masooleh, Irandokht; Hedayati Emami, Mohammad Hassan; Ghavidel Parsa, Pooneh; Amir Maafi, Alireza

    2015-01-01

    Background: Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients. Objectives: We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it. Patients and Methods: In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant. Results: A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower

  15. The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves’ Disease

    PubMed Central

    Cho, Sun Wook; Bae, Jae Hyun; Noh, Gyeong Woon; Kim, Ye An; Moon, Min Kyong; Park, Kyoung Un; Song, Junghan; Yi, Ka Hee; Park, Do Joon; Chung, June-Key; Cho, Bo Youn; Park, Young Joo

    2015-01-01

    Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease. PMID:26650844

  16. The influence of folic acid supplementation on maternal and fetal bone turnover.

    PubMed

    Hossein-nezhad, Arash; Mirzaei, Khadijeh; Maghbooli, Zhila; Najmafshar, Azam; Larijani, Bagher

    2011-03-01

    The aim of our study was to investigate the relationship between maternal and fetal bone turnover markers and folic acid supplementation during pregnancy. In an observational study performed in Tehran University of Medical Sciences related hospitals, 113 healthy pregnant women with gestational age between 8 and 12 weeks and aged between 15 and 42 years were recruited and followed until delivery time. The participants were divided into two groups; women who took 1 mg of folic acid daily supplement from the beginning of the pregnancy until the end of the second trimester entered into group I and women who choose to continue their daily intake of folic acid until the delivery time entered into group II. The two groups were matched based on the maternal anthropometric data, energy, calcium and vitamin D intake. Following the delivery, venous blood samples were collected from mothers and umbilical cords of the neonates. Maternal and fetal serum concentrations of 25-hydroxy vitamin D3, PTH, osteocalcin (OC), crosslaps and maternal serum level of homocysteine, folate, soluble receptor activator of NF-kappaB ligand (sRANKL), osteoprotegerin (OPG), calcium, and phosphate were measured. Measured birth outcome parameters included weight, length, head circumference, appearance, and respiration. With regard to maternal assessment, the serum levels of OC and OPG and folate were significantly higher in group II compared to group I, while the serum levels of RANKL and homocysteine were significantly higher in group I. We did not find significant differences in serum levels of 25-OH vitamin D, PTH, crosslaps, calcium, or phosphate between the two groups. The neonates from mothers recruited in group II had higher (but not significantly) serum level of OC. We observed that the neonates born from mothers in group II had overall better birth outcome parameters and apgar scores compare to the neonates born from mothers in group I. Our results show that daily supplementation of folic

  17. Interrelationship between bone turnover markers and dietary calcium intake in pregnant women: a longitudinal study.

    PubMed

    Zeni, Susana N; Ortela Soler, Carlos R; Lazzari, Araceli; López, Laura; Suarez, Marisa; Di Gregorio, Silvana; Somoza, Julia I; de Portela, Maria L

    2003-10-01

    This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in betaCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = -0.47, P < 0.03; r = -0.41, P < 0.05; and r = -0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be

  18. Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover.

    PubMed

    Fung, Ellen B; Vichinsky, Elliott P; Kwiatkowski, Janet L; Huang, James; Bachrach, Laura K; Sawyer, Aenor J; Zemel, Babette S

    2011-06-01

    Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of

  19. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

    PubMed

    Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

    2015-10-01

    Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets. PMID:26218891

  20. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance

    PubMed Central

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    Background It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). Material/Methods We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. Results During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. Conclusions Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  1. Dietary arginine affects energy metabolism through polyamine turnover in juvenile Atlantic salmon (Salmo salar).

    PubMed

    Andersen, Synne M; Holen, Elisabeth; Aksnes, Anders; Rønnestad, Ivar; Zerrahn, Jens-Erik; Espe, Marit

    2013-12-14

    In the present study, quadruplicate groups of juvenile Atlantic salmon (Salmo salar) were fed plant protein-based diets with increasing arginine inclusions (range 28·8-37·4 g/kg DM) to investigate whether arginine supplementation affects growth and lipid accumulation through an elevated polyamine turnover. Dietary lysine was held at a constant concentration, just below the requirement. All other amino acids were balanced and equal in the diets. Arginine supplementation increased protein and fat accretion, without affecting the hepatosomatic or visceralsomatic indices. Dietary arginine correlated with putrescine in the liver (R 0·78, P= 0·01) and with ornithine in the muscle, liver and plasma (P= 0·0002, 0·003 and 0·0002, respectively). The mRNA of ornithine decarboxylase, the enzyme producing putrescine, was up-regulated in the white adipose tissue of fish fed the high-arginine inclusion compared with those fed the low-arginine diet. Concomitantly, spermidine/spermine-(N1)-acetyltransferase, the rate-limiting enzyme for polyamine turnover that consumes acetyl-CoA, showed an increased activity in the liver of fish fed the arginine-supplemented diets. In addition, lower acetyl-CoA concentrations were observed in the liver of fish fed the high-arginine diet, while ATP, which is used in the process of synthesising spermidine and spermine, did not show a similar trend. Gene expression of the rate-limiting enzyme for β-oxidation of long-chain fatty acids, carnitine palmitoyl transferase-1, was up-regulated in the liver of fish fed the high-arginine diet. Taken together, the data support that increased dietary arginine activates polyamine turnover and β-oxidation in the liver of juvenile Atlantic salmon and may act to improve the metabolic status of the fish. PMID:23656796

  2. Dietary arginine affects energy metabolism through polyamine turnover in juvenile Atlantic salmon (Salmo salar).

    PubMed

    Andersen, Synne M; Holen, Elisabeth; Aksnes, Anders; Rønnestad, Ivar; Zerrahn, Jens-Erik; Espe, Marit

    2013-12-14

    In the present study, quadruplicate groups of juvenile Atlantic salmon (Salmo salar) were fed plant protein-based diets with increasing arginine inclusions (range 28·8-37·4 g/kg DM) to investigate whether arginine supplementation affects growth and lipid accumulation through an elevated polyamine turnover. Dietary lysine was held at a constant concentration, just below the requirement. All other amino acids were balanced and equal in the diets. Arginine supplementation increased protein and fat accretion, without affecting the hepatosomatic or visceralsomatic indices. Dietary arginine correlated with putrescine in the liver (R 0·78, P= 0·01) and with ornithine in the muscle, liver and plasma (P= 0·0002, 0·003 and 0·0002, respectively). The mRNA of ornithine decarboxylase, the enzyme producing putrescine, was up-regulated in the white adipose tissue of fish fed the high-arginine inclusion compared with those fed the low-arginine diet. Concomitantly, spermidine/spermine-(N1)-acetyltransferase, the rate-limiting enzyme for polyamine turnover that consumes acetyl-CoA, showed an increased activity in the liver of fish fed the arginine-supplemented diets. In addition, lower acetyl-CoA concentrations were observed in the liver of fish fed the high-arginine diet, while ATP, which is used in the process of synthesising spermidine and spermine, did not show a similar trend. Gene expression of the rate-limiting enzyme for β-oxidation of long-chain fatty acids, carnitine palmitoyl transferase-1, was up-regulated in the liver of fish fed the high-arginine diet. Taken together, the data support that increased dietary arginine activates polyamine turnover and β-oxidation in the liver of juvenile Atlantic salmon and may act to improve the metabolic status of the fish.

  3. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We

  4. Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children.

    PubMed

    Thiering, E; Brüske, I; Kratzsch, J; Hofbauer, L C; Berdel, D; von Berg, A; Lehmann, I; Hoffmann, B; Bauer, C P; Koletzko, S; Heinrich, J

    2015-01-01

    Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and β-Crosslaps (β-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and β-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in β-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the β-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and β-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker β-CTx was observed. PMID:26667774

  5. Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice.

    PubMed

    Alund, Alexander W; Mercer, Kelly E; Suva, Larry J; Pulliam, Casey F; Chen, Jin-Ran; Badger, Thomas M; Van Remmen, Holly; Ronis, Martin J J

    2016-07-01

    Chronic ethyl alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons of 6-week-old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (P < 0.05). Six-week-old wild-type (WT) and TgCAT female mice were chow fed or pair fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair feeding of WT had no demonstrable effect on the skeleton; however, EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared with PF controls (P < 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross-sectional area in TgCAT mice than WT mice (P < 0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less collagen1α and higher sclerostin mRNA (P < 0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. EtOH feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone turnover in an age-dependent manner, and indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia. PMID:27189961

  6. Mechanical property and tissue mineral density differences among severely suppressed bone turnover (SSBT) patients, osteoporotic patients, and normal subjects.

    PubMed

    Tjhia, Crystal K; Odvina, Clarita V; Rao, D Sudhaker; Stover, Susan M; Wang, Xiang; Fyhrie, David P

    2011-12-01

    Pathogenesis of atypical fractures in patients on long term bisphosphonate therapy is poorly understood, and the type, the manner in which they occur and the fracture sites are quite different from the usual osteoporotic fractures. We hypothesized that the tissue-level mechanical properties and mean degree of mineralization of the iliac bone would differ among 1) patients with atypical fractures and severely suppressed bone turnover (SSBT) associated with long-term bisphosphonate therapy, 2) age-matched, treatment-naïve osteoporotic patients with vertebral fracture, 3) age-matched normals and 4) young normals. Large differences in tissue-level mechanical properties and/or mineralization among these groups could help explain the underlying mechanism(s) for the occurrence of typical osteoporotic and the atypical femoral shaft fractures. Elastic modulus, contact hardness, plastic deformation resistance, and tissue mineral densities of cortical and trabecular bone regions of 55 iliac bone biopsies--12 SSBT patients (SSBT; aged 49-77), 11 age-matched untreated osteoporotic patients with vertebral fracture (Osteoporotic), 12 age-matched subjects without bone fracture (Age-Matched Normal), and 20 younger subjects without bone fracture (Young Normal)--were measured using nanoindentation and quantitative backscattered electron microscopy. For cortical bone nanoindentation properties, only plastic deformation resistance was different among the groups (p<0.05), with greater resistance to plastic deformation in the SSBT group compared to all other groups. For trabecular bone, all nanoindentation properties and mineral density of the trabecular bone were different among the groups (p<0.05). The SSBT group had greater plastic deformation resistance and harder trabecular bone compared to the other three groups, stiffer bone compared to the Osteoporotic and Young Normal groups, and a trend of higher mineral density compared to the Age-Matched Normal and Osteoporotic groups. Lower

  7. Daily Parathyroid Hormone 1-34 Replacement Therapy for Hypoparathyroidism Induces Marked Changes in Bone Turnover and Structure

    PubMed Central

    Gafni, Rachel I.; Brahim, Jaime S.; Andreopoulou, Panagiota; Bhattacharyya, Nisan; Kelly, Marilyn H.; Brillante, Beth A.; Reynolds, James C.; Zhou, Hua; Dempster, David W.; Collins, Michael T.

    2012-01-01

    Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic leading to osteoporosis, yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated five hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected 2-3 times daily for 18 months, with doses individualized to maintain serum calcium at 1.9-2.25 mmol/L. Biochemical markers and bone density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged, however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased, however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in

  8. Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy prote...

  9. Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

    PubMed Central

    Ruan, Jianwei; Gong, Xiaokang; Kong, Jinsong; Wang, Haibao; Zheng, Xin; Chen, Tao

    2015-01-01

    Background B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies. Material/Methods Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation. Results Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover. Conclusions B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future. PMID:25805360

  10. Effects of Sigma Anti-bonding Molecule Calcium Carbonate on bone turnover and calcium balance in ovariectomized rats.

    PubMed

    Choi, So-Young; Park, Dongsun; Yang, Goeun; Lee, Sun Hee; Bae, Dae Kwon; Hwang, Seock-Yeon; Lee, Paul K; Kim, Yun-Bae; Kim, Ill-Hwa; Kang, Hyun-Gu

    2011-12-01

    This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

  11. Is Gastrectomy-Induced High Turnover of Bone with Hyperosteoidosis and Increase of Mineralization a Typical Osteomalacia?

    PubMed Central

    Ueyama, Takashi; Yamamoto, Yuta; Ueda, Kazuki; Yajima, Aiji; Maeda, Yoshimasa; Yamashita, Yasunobu; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

    2013-01-01

    Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone. PMID:23776526

  12. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal

  13. Water level changes affect carbon turnover and microbial community composition in lake sediments.

    PubMed

    Weise, Lukas; Ulrich, Andreas; Moreano, Matilde; Gessler, Arthur; Kayler, Zachary E; Steger, Kristin; Zeller, Bernd; Rudolph, Kristin; Knezevic-Jaric, Jelena; Premke, Katrin

    2016-05-01

    Due to climate change, many lakes in Europe will be subject to higher variability of hydrological characteristics in their littoral zones. These different hydrological regimes might affect the use of allochthonous and autochthonous carbon sources. We used sandy sediment microcosms to examine the effects of different hydrological regimes (wet, desiccating, and wet-desiccation cycles) on carbon turnover. (13)C-labelled particulate organic carbon was used to trace and estimate carbon uptake into bacterial biomass (via phospholipid fatty acids) and respiration. Microbial community changes were monitored by combining DNA- and RNA-based real-time PCR quantification and terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA. The shifting hydrological regimes in the sediment primarily caused two linked microbial effects: changes in the use of available organic carbon and community composition changes. Drying sediments yielded the highest CO2 emission rates, whereas hydrological shifts increased the uptake of allochthonous organic carbon for respiration. T-RFLP patterns demonstrated that only the most extreme hydrological changes induced a significant shift in the active and total bacterial communities. As current scenarios of climate change predict an increase of drought events, frequent variations of the hydrological regimes of many lake littoral zones in central Europe are anticipated. Based on the results of our study, this phenomenon may increase the intensity and amplitude in rates of allochthonous organic carbon uptake and CO2 emissions. PMID:26902802

  14. Water level changes affect carbon turnover and microbial community composition in lake sediments

    PubMed Central

    Weise, Lukas; Ulrich, Andreas; Moreano, Matilde; Gessler, Arthur; E. Kayler, Zachary; Steger, Kristin; Zeller, Bernd; Rudolph, Kristin; Knezevic-Jaric, Jelena; Premke, Katrin

    2016-01-01

    Due to climate change, many lakes in Europe will be subject to higher variability of hydrological characteristics in their littoral zones. These different hydrological regimes might affect the use of allochthonous and autochthonous carbon sources. We used sandy sediment microcosms to examine the effects of different hydrological regimes (wet, desiccating, and wet-desiccation cycles) on carbon turnover. 13C-labelled particulate organic carbon was used to trace and estimate carbon uptake into bacterial biomass (via phospholipid fatty acids) and respiration. Microbial community changes were monitored by combining DNA- and RNA-based real-time PCR quantification and terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA. The shifting hydrological regimes in the sediment primarily caused two linked microbial effects: changes in the use of available organic carbon and community composition changes. Drying sediments yielded the highest CO2 emission rates, whereas hydrological shifts increased the uptake of allochthonous organic carbon for respiration. T-RFLP patterns demonstrated that only the most extreme hydrological changes induced a significant shift in the active and total bacterial communities. As current scenarios of climate change predict an increase of drought events, frequent variations of the hydrological regimes of many lake littoral zones in central Europe are anticipated. Based on the results of our study, this phenomenon may increase the intensity and amplitude in rates of allochthonous organic carbon uptake and CO2 emissions. PMID:26902802

  15. Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

    PubMed

    Kristensen, Mette; Jensen, Marlene; Kudsk, Jane; Henriksen, Marianne; Mølgaard, Christian

    2005-12-01

    In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

  16. Effects of Pegylated Interferon/Ribavirin on Bone Turnover Markers in HIV/Hepatitis C Virus-Coinfected Patients

    PubMed Central

    Kang, Minhee; Tebas, Pablo; Overton, Edgar T.; Hollabaugh, Kimberly; McComsey, Grace; Bhattacharya, Debika; Evans, Christopher; Brown, Todd T.; Taiwo, Babafemi

    2016-01-01

    Abstract HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: −120 pg/ml and −8.48 μg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions. PMID:26499270

  17. Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover.

    PubMed

    Kruger, Marlena C; Kruger, Iolanthé M; Wentzel-Viljoen, Edelweiss; Kruger, Annamarie

    2011-10-01

    Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women.

  18. Associations between ambient air pollution and bone turnover markers in 10-year old children: results from the GINIplus and LISAplus studies.

    PubMed

    Liu, Chuang; Fuertes, Elaine; Flexeder, Claudia; Hofbauer, Lorenz C; Berdel, Dietrich; Hoffmann, Barbara; Kratzsch, Jürgen; von Berg, Andrea; Heinrich, Joachim

    2015-01-01

    Negative associations between bone turnover markers and bone mineral density have been reported. In order to study the association between ambient air pollution and bone turnover markers, as indicators of bone loss, we investigated associations between land-use regression modeled air pollution (NO2, PM2.5 mass, PM2.5 - 10 [coarse particles], PM10 mass and PM2.5 absorbance) and bone turnover markers in 2264 children aged 10 years. Serum osteocalcin and C-terminal telopeptide of type I collagen (CTx), measured by Modular-System (Roche), were the two bone turnover markers considered in this analysis. In total population, NO2, PM2.5 - 10 and PM10 mass exposure were positively and significantly associated with both osteocalcin and CTx. A 2.5 (95% CI: 0.6, 4.4) ng/ml increase in osteocalcin and a 24.0 (95% CI: 6.7, 41.3) ng/L increase in CTx were observed per IQR (6.7μg/m(3)) increase in NO2, independent of socioeconomic status, sex, age, pubertal status, fasting status and total physical activity. The estimated coefficients were 3.0 (95% CI: 0.1, 5.8) for osteocalcin and 32.3 (95% CI: 6.1, 58.5) for CTx with PM2.5 - 10; 3.2 (95% CI: 0.0, 6.4) for osteocalcin and 30.7 (95% CI: 1.7, 59.7) for CTx with PM10. Children living close to a major road (≤ 350m) had higher levels of both osteocalcin (1.4 [-1.2, 4.0] ng/ml) and CTx (16.2 [-7.4, 39.8] ng/L). The adverse impact of ambient air pollution on bone turnover rates observed in one of the study areas showed stimulation of more such studies.

  19. Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

    PubMed

    Fiore, C E; Pennisi, P; DiStefano, A; Riccobene, S; Caschetto, S

    2003-05-01

    Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption. PMID:12916002

  20. Supplementation of L-arginine prevents glucocorticoid-induced reduction of bone growth and bone turnover abnormalities in a growing rat model.

    PubMed

    Pennisi, Pietra; D'Alcamo, Maria Antonia; Leonetti, Concetta; Clementi, Anna; Cutuli, Vincenza Maria; Riccobene, Stefania; Parisi, Natalia; Fiore, Carmelo Erio

    2005-01-01

    The present study was designed to evaluate the effects of glucocorticoid (GC) treatment on bone turnover and bone mineral density in the growing rat. Because of the recent evidence that nitric oxide (NO) can counteract prednisolone-induced bone loss in mature rats, we examined the effect on bone of the NO donor L: -arginine in young male rats, in which bone mass is increased by the same biological mechanism as in children and adolescents. Thirty-six 10-week-old Sprague-Dawley male rats were assigned to six groups of six animals each, and treated for 4 weeks with either vehicle (once a week subcutaneous injection of 100 microl of sesame oil); prednisolone sodium succinate, 5 mg/kg, 5 days per week by intramuscular injection (i.m.); L-arginine, 10 mg/kg intraperitoneally (i.p.) once a day; N(G)-nitro-L-arginine methylester (L-NAME), 50 mg/kg subcutaneously once a day; prednisolone sodium succinate 5 mg/kg, 5 days per week i.m. +L-arginine 10 mg/kg i.p. once a day; or prednisolone sodium succinate, 5 mg/kg, 5 days per week i.m. +L-NAME 50 mg/kg subcutaneously once a day. Serum calcium, alkaline phosphatase (ALP), osteocalcin, and the C-terminal telopeptides of type I collagen (RatLaps) were measured at baseline conditions and after 2 and 4 weeks. Prior to treatment, and after 2 and 4 weeks, the whole body, vertebral, pelvic, and femoral bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) scanning. Prednisolone and prednisolone+L-NAME treated rats had significantly lower ALP and osteocalcin levels than controls at 2 and 4 weeks, and significantly higher levels of Rat-Laps than controls at 4 weeks. Prednisolone, L-NAME, and prednisolone+L-NAME produced a significant inhibition of bone accumulation and bone growth at all sites measured. Supplementation with L-arginine appeared to prevent the inhibition of bone growth and increase in bone resorption induced by prednisolone. These data would suggest, for the first time, that supplementation

  1. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group.

    PubMed

    Chapuy, M C; Schott, A M; Garnero, P; Hans, D; Delmas, P D; Meunier, P J

    1996-03-01

    It was recently demonstrated that calcium and vitamin D supplements were capable of decreasing the incidence of hip fractures in institutionalized elderly subjects through a reduction of senile secondary hyperparathyroidism. As there are no appropriate data to recommend such a supplement to the elderly living at home, the aim of this study was to determine the incidence of senile secondary hyperparathyroidism in old French women from the general community, its relation to vitamin D status, and its contribution to bone turnover. Four hundred and forty women, aged 75-90 yr, were randomly selected from the general community by mailing from electoral listing in 5 French cities whose latitude varies from 49 degrees 9N to 43 degrees 6N. At the end of the winter, with previous hip fractures or those who were institutionalized were excluded. The results obtained in these women were compared to those obtained in 59 institutionalized old women and 54 younger healthy women. In the five cities for the women living at home, we found a mean PTH value greater than that obtained in young women (63 +/- 28 vs. 43 +/- 15 pg/ml; P = 0.001), but lower that that found in institutionalized women (76 +/- 49 pg/mL; P = 0.05). The mean 25-hydroxyvitamin D (25OHD) level was not different in subjects from the 5 cities, but in all of them it was significantly greater than that found in 59 institutionalized women (42.5 +/- 25.0 vs. 15.5 +/- 6.5 nmol/L; P = 0.0001) but lower than that in young adults (P < 0.001). The main determinants of PTH were in equal ratio, i.e. age (r = 0.19; P < 0.001), 25OHD, and, to a lesser degree, creatinine clearance (r = 0.10; P = 0.03). For 25OHD, the main determinant was the personal outdoor score and, to a lesser extent, the amount of daily sunlight in the city. The mean values of biochemical markers of bone turnover, bone alkaline phosphatase, osteocalcin, and Crosslaps, were significantly increased compared with the results obtained in young women, and

  2. Biochemical Markers of Bone Turnover Part II: Clinical Applications in the Management of Osteoporosis

    PubMed Central

    Seibel, Markus J

    2006-01-01

    With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This second part of the two part series reviews the current evidence regarding the clinical use of biochemical markers of bone remodelling in the management of osteoporosis. PMID:17268581

  3. Bone calcium turnover during pregnancy and lactation in women with low calcium diets is associated with calcium intake and circulating insulin-like growth factor 1 concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Few data exist on longitudinal changes in bone calcium turnover rates across pregnancy and lactation. OBJECTIVE: Our aim was to characterize calcium kinetic variables and predictors of these changes across pregnancy and early lactation in women with low calcium intakes. DESIGN: Stable ca...

  4. Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Gilhooly, Cheryl H; Shea, M Kyla; Fielding, Roger A; Ceglia, Lisa

    2016-01-01

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p =0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p =0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed. PMID:25990255

  5. Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Gilhooly, Cheryl H; Shea, M Kyla; Fielding, Roger A; Ceglia, Lisa

    2015-11-01

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3 ) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed.

  6. Alteration of proteoglycan sulfation affects bone growth and remodeling

    PubMed Central

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-01-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. PMID:23369989

  7. Effect of chronic activity-based therapy on bone mineral density and bone turnover in persons with spinal cord injury

    PubMed Central

    Harness, Eric T.; Witzke, Kara A.

    2014-01-01

    Purpose Osteoporosis is a severe complication of spinal cord injury (SCI). Many exercise modalities are used to slow bone loss, yet their efficacy is equivocal. This study examined the effect of activity-based therapy (ABT) targeting the lower extremities on bone health in individuals with SCI. Methods Thirteen men and women with SCI (age and injury duration = 29.7 ± 7.8 and 1.9 ± 2.7 years) underwent 6 months of ABT. At baseline and after 3 and 6 months of training, blood samples were obtained to assess bone formation (serum procollagen type 1 N propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans to obtain total body and regional estimates of bone mineral density (BMD). Results Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8 %; 1.27 ± 0.22–1.33 ± 0.24 g/cm2) and decreases (p < 0.01) in total hip BMD (−6.1 %; 0.98 ± 0.18–0.91 ± 0.16 g/cm2) from 0 to 6 months of training. BMD at the bilateral distal femur (−7.5 to −11.0 %) and proximal tibia (− 8.0 to −11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP nor CTX was altered (p> 0.05) with training. Conclusions Chronic activity-based therapy did not reverse bone loss typically observed soon after injury, yet reductions in BMD were less than the expected magnitude of decline in lower extremity BMD in persons with recent SCI. PMID:24097172

  8. Role of B₁₂ and homocysteine status in determining BMD and bone turnover in young Indians.

    PubMed

    Haroon, Nisha Nigil; Marwaha, Raman K; Godbole, Madan M; Gupta, Sushil K

    2012-01-01

    Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 μmol/L (IQR 14-32 μmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 μmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.

  9. 1-alpha-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women.

    PubMed

    Chen, J T; Shiraki, M; Hasumi, K; Tanaka, N; Katase, K; Kato, T; Hirai, Y; Nakamura, T; Ogata, E

    1997-06-01

    50 Japanese women within 10 years after menopause (mean age 52.5 years) were studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3 [1-alpha-(OH)D3] with calcium (150 mg/day) (treated group: N = 25) and calcium only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2-4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal women. L2-4 BMDs increased significantly in the treated group (+2.1%; p < 0.01), but decreased significantly in controls (-2.1%; p < 0.01). Although serum calcium and creatinine remained unchanged in both groups, phosphorus levels increased significantly in the treated group (p < 0.01). Urinary calcium/creatinine (Cr) increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group (p < 0.05), but not in the control group. Serum osteocalcin levels remained unchanged in both groups. Intact parathyroid hormone levels decreased significantly (p < 0.05) and calcitonin levels significantly increased in the treated group (p < 0.05), but these changes were not observed in the control group. These data clearly demonstrate that 0.75 microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones. Temporarily increased urinary calcium excretion was observed in control group, but did not appear to be effective in modulating bone turnover. PMID:9177871

  10. Tooth dentin defects reflect genetic disorders affecting bone mineralization

    PubMed Central

    Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

    2012-01-01

    Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

  11. Three-dimensional assessment of bone turnover using computed microtomography and laser-scanning confocal microscopy

    NASA Astrophysics Data System (ADS)

    Prevrhal, Sven; Jiang, Yebin; Zhao, Jenny; Genant, Harry K.

    2000-06-01

    Objective: Metabolic activity in trabecular bone is an important indicator in the therapy of bone diseases like osteoporosis. It is reflected by the amount of osteoid (young, not yet mineralized bone) and young calcified tissue (YCT). Our aim was to replace standard 2D histomorphometry with a 3D approach for osteoid and YCT measurement. Measurement Methods: Excised lumbar vertebrae of 5 ovariectomized (OVX) and 5 control rats were 3D-scanned with computed micro-tomography ((mu) CT, isotropic spatial resolution 20 micrometer3) and laser scanning confocal microscopy (LSCM, 20X magnification, 1X1X2 micrometer3 spatial resolution). (mu) CT shows trabecular bone structure; LSCM shows osteoid and YCT by fluorescent light. Image Processing Methods: The fraction of bone to tissue volume (BV/TV) and the number of trabeculae (Tb.N) were calculated from globally thresholded (mu) CT images. LSCM images were enhanced using top-hat transform, globally thresholded and morphologically closed. Separate regions were labeled by volume growing. We measured feature volume to background volume ratio and number of features per unit volume. Results and Conclusions: In the specimens obtained from the OVX rats, a significant increase in the volume fractions of osteoid and YCT could be seen. The (mu) CT-LSCM approach presents a significant improvement over time-consuming, standard histomorphometry. The image processing for both modalities could be achieved automatically.

  12. The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women.

    PubMed

    Hwang, You-Cheol; Jeong, In-Kyung; Ahn, Kyu Jeung; Chung, Ho Yeon

    2009-01-01

    The purpose of this prospective randomized study was to investigate the effects of the extract of Acanthopanax senticosus (AS extract), a widely used oriental herb, on bone remodeling and bone mineral density in Korean postmenopausal women. A total of 81 postmenopausal women with osteopenia or osteoporosis, an age of less than 65 years, were enrolled in the study. Subjects were randomly assigned to two groups: (1) the control group (n = 40), calcium intake (500 mg per day), and (2) the treatment group (n = 41), calcium (500 mg per day) plus AS extract (3 g per day). After treatment with AS extract for 6 months, the AS extract group showed a significant increase in serum osteocalcin levels compared with the control group (P = 0.041). However, no significant changes in bone mineral density were observed by dual-energy X-ray absorptiometry (DXA). AS extract was generally well tolerated, and no differences were observed between the two groups in terms of adverse events. This study suggests that AS extract supplementation may have beneficial effects on bone remodeling in Korean postmenopausal women and that it has no significant adverse events.

  13. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives.

    PubMed

    He, Feng J; Marciniak, Maciej; Carney, Christine; Markandu, Nirmala D; Anand, Vidya; Fraser, William D; Dalton, R Neil; Kaski, Juan C; MacGregor, Graham A

    2010-03-01

    To determine the effects of potassium supplementation on endothelial function, cardiovascular risk factors, and bone turnover and to compare potassium chloride with potassium bicarbonate, we carried out a 12-week randomized, double-blind, placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure. Urinary potassium was 77+/-16, 122+/-25, and 125+/-27 mmol/24 hours after 4 weeks on placebo, potassium chloride, and potassium bicarbonate, respectively. There were no significant differences in office blood pressure among the 3 treatment periods, and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride. Compared with placebo, both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation, increased arterial compliance as assessed by carotid-femoral pulse wave velocity, decreased left ventricular mass, and improved left ventricular diastolic function. There was no significant difference between the 2 potassium salts in these measurements. The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin:creatinine ratio, and potassium bicarbonate decreased 24-hour urinary calcium, calcium:creatinine ratio, and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly. These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system, and potassium bicarbonate may improve bone health. Importantly, these effects were found in individuals who already had a relatively low-salt and high-potassium intake.

  14. Adequate dietary vitamin D and calcium are both required to reduce bone turnover and increased bone mineral volume.

    PubMed

    Lee, Alice M C; Sawyer, Rebecca K; Moore, Alison J; Morris, Howard A; O'Loughlin, Peter D; Anderson, Paul H

    2014-10-01

    Clinical studies indicate that the combination of vitamin D and dietary calcium supplementation is more effective for reducing fracture risk than either supplement alone. Our previous dietary studies demonstrated that an adequate serum 25-hydroxyvitamin D3 (25D) of 80nmol/L or more reduces bone RANKL expression, osteoclastogenesis and maintains the optimal levels of trabecular bone volume (BV/TV%) in young rats. The important clinical question of the interaction between vitamin D status, dietary calcium intake and age remains unclear. Hence, 9 month-old female Sprague-Dawley rats (n=5-6/group) were pair-fed a semi-synthetic diet containing varying levels of vitamin D (0, 2, 12 or 20IU/day) and dietary calcium (0.1% or 1%) for 6 months. At 15 months of age, animals were killed, for biochemical and skeletal analyses. While changes to serum 25D were determined by both dietary vitamin D and calcium levels, changes to serum 1,25-dihydroxyvitamin D3 (1,25D) were consistently raised in animals fed 0.1% Ca regardless of dietary vitamin D or vitamin D status. Importantly, serum cross-laps levels were significantly increased in animals fed 0.1% Ca only when combined with 0 or 2 IUD/day of vitamin D, suggesting a contribution of both dietary calcium and vitamin D in determining bone resorption activity. Serum 25(OH)D3 levels were positively correlated with both femoral mid-diaphyseal cortical bone volume (R(2)=0.24, P<0.01) and metaphyseal BV/TV% (R(2)=0.23, P<0.01, data not shown). In multiple linear regressions, serum 1,25(OH)2D3 levels were a negative determinant of CBV (R(2)=0.24, P<0.01) and were not a determinant of metaphyseal BV/TV% levels. These data support clinical data that reduced bone resorption and increased bone volume can only be achieved with adequate 25D levels in combination with high dietary calcium and low serum 1,25D levels. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24309068

  15. ROS/redox signaling regulates bone turnover in an age-specific manner in female mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide appears to be an important stimulus for osteoclast differentiation and activity. ROS signaling has been suggested to increase RANKL mRNA and protein expression, thus enha...

  16. Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

    1994-01-01

    The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

  17. Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

    1994-01-01

    The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate, (the distal tibial metaphysis (DTM), to ovariectomy (OVX) and OVX plus a prostaglandin E(2) treatment, and compare the site's response to previous findings reported for another site, the proximal tibial metaphysis (PTM). Thirty five 3-month old female Sprague-Dawley rats were divided into five groups; basal, sham OVX, and OVX+0, +1, or +6 mg PGE(2)/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20 micrometer thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months POST OVX there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE(2)/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE(2)/kd/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation, without altering bone resportion. Futhermore, After PGE(2) admimnistration, the DTM, a cancellous bone site with a closed growth plate, increased bone formation more than did the cancellous bone in the PTM.

  18. Nitrogen stress affects the turnover and size of nitrogen pools supplying leaf growth in a grass.

    PubMed

    Lehmeier, Christoph Andreas; Wild, Melanie; Schnyder, Hans

    2013-08-01

    The effect of nitrogen (N) stress on the pool system supplying currently assimilated and (re)mobilized N for leaf growth of a grass was explored by dynamic ¹⁵N labeling, assessment of total and labeled N import into leaf growth zones, and compartmental analysis of the label import data. Perennial ryegrass (Lolium perenne) plants, grown with low or high levels of N fertilization, were labeled with ¹⁵NO₃⁻/¹⁴NO₃⁻ from 2 h to more than 20 d. In both treatments, the tracer time course in N imported into the growth zones fitted a two-pool model (r² > 0.99). This consisted of a "substrate pool," which received N from current uptake and supplied the growth zone, and a recycling/mobilizing "store," which exchanged with the substrate pool. N deficiency halved the leaf elongation rate, decreased N import into the growth zone, lengthened the delay between tracer uptake and its arrival in the growth zone (2.2 h versus 0.9 h), slowed the turnover of the substrate pool (half-life of 3.2 h versus 0.6 h), and increased its size (12.4 μg versus 5.9 μg). The store contained the equivalent of approximately 10 times (low N) and approximately five times (high N) the total daily N import into the growth zone. Its turnover agreed with that of protein turnover. Remarkably, the relative contribution of mobilization to leaf growth was large and similar (approximately 45%) in both treatments. We conclude that turnover and size of the substrate pool are related to the sink strength of the growth zone, whereas the contribution of the store is influenced by partitioning between sinks.

  19. Clinical usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase activity in evaluating bone turnover.

    PubMed

    Nakanishi, M; Yoh, K; Uchida, K; Maruo, S; Rai, S K; Matsuoka, A

    1999-01-01

    This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

  20. Circulating levels of osteoclast activating cytokines, interleukin-11 and transforming growth factor-beta2, as valuable biomarkers for the assessment of bone turnover in postmenopausal osteoporosis.

    PubMed

    Shaarawy, Mohamed; Zaki, Sameh; Sheiba, Mamdouh; El-Minawi, Ahmad M

    2003-01-01

    The objective of this study was to evaluate the role of osteoclast activating cytokines, interleukin-11 (IL-11) and transforming growth factor-beta2 (TGF-beta2) in the assessment of bone turnover in postmenopausal osteoporosis (PO). Eighty postmenopausal osteoporotic women with lumbar spine bone mineral densities (BMD) as measured by DEXA that were more than 2.5 SD below the normal mean of healthy women (controls), participated in this study. Various therapeutic modalities (hormone replacement therapy, HRT, alendronate, calcitonin and 1alpha-hydroxyvitamin D (alfacalcidol) were administered for 12 months to 4 groups of postmenopausal osteoporotic patients. Fasting blood samples and two hour urine samples were collected from control subjects and from patients before and after treatment. Serum samples were assayed for IL-11, TGF-beta2, osteocalcin (OC) and bone alkaline phosphatase (B-ALP), whereas urine samples were assayed for N-telopeptide for type I collagen (NTX) and deoxypyridinoline (DPyr). The results demonstrated a significant increase of both IL-11 and TGF-beta2 in postmenopausal osteoporosis. Positive correlations exist between TGF-beta2 or IL-11 and markers of bone resorption (NTX and DPyr). Moreover, there was a significant positive correlation between TGF-beta2 and IL-11. Therapeutic modalities enhancing bone formation and/or with antiresorptive effect revealed a significant decrease in markers of bone resorption, formation and osteoclast activating cytokines, indicating a decrease in bone turnover. The decrease of IL-11 and TGF-beta2 may be attributed to a drug inhibitory effect of these cytokines on enhancing osteoblast mediated osteoid degradation. In conclusion, both serum IL-11 and TGF-beta2 determinations may be considered as biomarkers for the assessment of bone turnover and for monitoring antiresorptive therapy in postmenopausal osteoporosis.

  1. Spaceflight and bone turnover - Correlation with a new rat model of weightlessness

    NASA Technical Reports Server (NTRS)

    Morey, E. R.

    1979-01-01

    Earlier manned spaceflight studies have revealed that the near-weightless environment of orbital flight produce certain biological effects in humans, including abnormalities in mineral metabolism. The data collected were compatible with bone mineral loss. Cosmos 782 and 936 experiments have shown a decrease in rat bone formation rate. In this paper, a rat model of weightlessness is described, which is unique in that the animal is free to move about a 360-deg arc. The model meets the requirements for an acceptable system. Data from the model and spaceflight are presented. Many of the responses noted in suspended animals indicate that the model closely mimics results from rats and man exposed to near-weightlessness during orbital spaceflight.

  2. Bacterial community structure and carbon turnover in permafrost-affected soils of the Lena Delta, northeastern Siberia.

    PubMed

    Wagner, Dirk; Kobabe, Svenja; Liebner, Susanne

    2009-01-01

    Arctic permafrost environments store large amounts of organic carbon. As a result of global warming, intensified permafrost degradation and release of significant quantities of the currently conserved organic matter is predicted for high latitudes. To improve our understanding of the present and future carbon dynamics in climate sensitive permafrost ecosystems, the present study investigates structure and carbon turnover of the bacterial community in a permafrost-affected soil of the Lena Delta (72 degrees 22'N, 126 degrees 28'E) in northeastern Siberia. 16S rRNA gene clone libraries revealed the presence of all major soil bacterial groups and of the canditate divisions OD1 and OP11. A shift within the bacterial community was observed along the soil profile indicated by the absence of Alphaproteobacteria and Betaproteobacteria and a simultaneous increase in abundance and diversity of fermenting bacteria like Firmicutes and Actinobacteria near the permafrost table. BIOLOG EcoPlates were used to describe the spectrum of utilized carbon sources of the bacterial community in different horizons under in situ temperature conditions in the presence and absence of oxygen. The results revealed distinct qualitative differences in the substrates used and the turnover rates under oxic and anoxic conditions. It can be concluded that constantly negative redox potentials as characteristic for the near permafrost table horizons of the investigated soil did effectively shape the structure of the indigenous bacterial community limiting its phylum-level diversity and carbon turnover capacity.

  3. Serum Sclerostin Levels in Patients with Human Immunodeficiency Virus Infection and Their Association with Bone Turnover Markers and Bone Mineral Densitometry

    PubMed Central

    Abdulfatah, Mohammed E.; Baaqil, Omar H.; Bakheet, Alaa A.; Turki, Sarah A.; Kotb, Mamdouh M.; Althubaiti, Alaa; Almaghrabi, Majed M.; Althubaiti, Abdulrahman M.; Madani, Badr M.; Jawad, Ali S. M.

    2016-01-01

    Background The aim of the study was to compare serum sclerostin levels in human im-munodeficiency virus (HIV)-infected patients and healthy controls, and to evaluate their relationship with bone turnover markers (BTM) and bone mineral density (BMD). Methods We prospectively studied 33 HIV treatment-naive patients and 63 healthy individuals; matched for age and sex. Serum sclerostin levels, BTM, BMD were measured. Viral load and cluster of differentiation 4 (CD4) levels were also assessed in HIV-infected patients. Results The mean±standard deviation (SD) age of sample was 37.6±10.3 years (range, 19 to 59 years). Of the 96 subjects, 58 (60.4%) were male and 38 (39.6%) were female. Infection with HIV is associated with significant reduction in serum sclerostin levels (HIV-infected: 39.4±28.3 vs. non HIV: 76.6±15.7 pmol/L; P<0.001) and a decrease in BMD at femoral neck and lumbar spine compared to healthy controls. Sclerostin however was not correlated with BMD and was not related to age, generally a strong correlation. There were no significant correlations between sclerostin and BTM (P>0.05). Conclusions These findings suggest that untreated HIV and the resulting immune deficiency and/or systemic inflammation could be an important regulator of serum sclerostin in this population. PMID:26981516

  4. Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

    PubMed Central

    2012-01-01

    Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

  5. Turnover Begets Turnover

    ERIC Educational Resources Information Center

    Castle, Nicholas G.

    2005-01-01

    Purpose: This study examined the association between turnover of caregivers and turnover of nursing home top management. The top managers examined were administrators and directors of nursing, and the caregivers examined were registered nurses, licensed practical nurses, and nurse aides. Design and Methods: The data came from a survey of 419…

  6. Serum Sema4D levels are associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis

    PubMed Central

    Zhang, Yiyuan; Feng, Eryou; Xu, Yang; Wang, Wulian; Zhang, Tao; Xiao, Lili; Chen, Rong; Lin, Yu; Chen, Dongdong; Lin, Liqiong; Chen, Kangyao; Lin, Yanbin

    2015-01-01

    To investigate the association of serum semaphorin 4D (Sema4D) levels with lumbar spine bone mineral density (BMD) and bone turnover markers in patients with postmenopausal osteoporosis (PO). Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 257 PO patients (aged from 50 to 75) and 90 healthy controls (aged from 51 to 83). Serum Sema4D, BAP, BGP and TRACP-5b levels were measured by enzyme linked immunosorbent assay. Serum cross linked N-telopeptides of type I (NTX), 25-hydroxyvitamin D (25(OH)D) and N-mid fragment of osteocalcin (N-MID-OT) levels were measured using automated electrochemiluminescence system. Sema4D level was significantly higher in PO women compared to healthy controls (1.40±0.33 vs. 0.58±0.18 μg/L, P=0.006). Sema4D level was positively correlated with serumTRACP-5b and NTX levels and negatively correlated with lumbar spine BMD and serum BAP and BGP levels. There were no correlations between Sema4D level and age, body mass index, and serum 25(OH)D and N-MID-OT levels. Lumbar spine BMD (β=-0.354, P<0.001) and serum BAP level (β=0.127, P=0.019) were independent predictors of serum Sema4D level in PO patients. Sema4D may be involved in the pathogenesis of PO and play a critical role in bone formation and resorption. Sema4D may represent a novel therapeutic target for treatment of PO and function as a predictive indicator of PO. PMID:26629156

  7. Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

    PubMed

    Saito, Mitsuru; Grynpas, Marc D; Burr, David B; Allen, Matthew R; Smith, Susan Y; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi

    2015-04-01

    Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage

  8. Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys.

    PubMed

    Kostenuik, Paul J; Smith, Susan Y; Samadfam, Rana; Jolette, Jacquelin; Zhou, Lei; Ominsky, Michael S

    2015-04-01

    Postmenopausal osteoporosis is a chronic disease wherein increased bone remodeling reduces bone mass and bone strength. Antiresorptive agents including bisphosphonates are commonly used to mitigate bone loss and fracture risk. Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer approach for reducing fracture risk in patients at increased risk for fracture. The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One day after OVX, cynos (7-10/group) were treated with vehicle (VEH, s.c.), ALN (50 μg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other animals received VEH or ALN for 6 months and then transitioned to 6 months of DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and transition from ALN to DMAb caused further reductions relative to continued ALN. DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb resulted in a lesser decline in Ca relative to DMAb or to VEH-DMAb transition. Bone histomorphometry indicated significantly reduced trabecular and cortical remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling, and transition from ALN to DMAb reduced these parameters relative to continued ALN. Bone mineral density increased in all active treatment groups relative to VEH controls. Destructive biomechanical testing revealed significantly greater vertebral strength in all three groups receiving DMAb, including those receiving DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly correlated in all groups at all tested skeletal sites, consistent with normal bone quality. These data indicate that cynos transitioned from ALN to DMAb exhibited reduced bone resorption and cortical porosity, and increased BMD and bone strength, without

  9. Osteoprogenitor cells from bone marrow and cortical bone: understanding how the environment affects their fate.

    PubMed

    Corradetti, Bruna; Taraballi, Francesca; Powell, Sebastian; Sung, David; Minardi, Silvia; Ferrari, Mauro; Weiner, Bradley K; Tasciotti, Ennio

    2015-05-01

    Bone is a dynamic organ where skeletal progenitors and hematopoietic cells share and compete for space. Presumptive mesenchymal stem cells (MSC) have been identified and harvested from the bone marrow (BM-MSC) and cortical bone fragments (CBF-MSC). In this study, we demonstrate that despite the cells sharing a common ancestor, the differences in the structural properties of the resident tissues affect cell behavior and prime them to react differently to stimuli. Similarly to the bone marrow, the cortical portion of the bone contains a unique subset of cells that stains positively for the common MSC-associated markers. These cells display different multipotent differentiation capability, clonogenic expansion, and immunosuppressive potential. In particular, when compared with BM-MSC, CBF-MSC are bigger in size, show a lower proliferation rate at early passages, have a greater commitment toward the osteogenic lineage, constitutively produce nitric oxide as a mediator for bone remodeling, and more readily respond to proinflammatory cytokines. Our data suggest that the effect of the tissue's microenvironment makes the CBF-MSC a superior candidate in the development of new strategies for bone repair.

  10. Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

    PubMed Central

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

  11. Habitat Heterogeneity Affects Plant and Arthropod Species Diversity and Turnover in Traditional Cornfields

    PubMed Central

    Martínez, Eliana; Rös, Matthias; Bonilla, María Argenis; Dirzo, Rodolfo

    2015-01-01

    The expansion of the agricultural frontier by the clearing of remnant forests has led to human-dominated landscape mosaics. Previous studies have evaluated the effect of these landscape mosaics on arthropod diversity at local spatial scales in temperate and tropical regions, but little is known about fragmentation effects in crop systems, such as the complex tropical traditional crop systems that maintain a high diversity of weeds and arthropods in low-Andean regions. To understand the factors that influence patterns of diversity in human-dominated landscapes, we investigate the effect of land use types on plant and arthropod diversity in traditionally managed cornfields, via surveys of plants and arthropods in twelve traditional cornfields in the Colombian Andes. We estimated alpha and beta diversity to analyze changes in diversity related to land uses within a radius of 100 m to 1 km around each cornfield. We observed that forests influenced alpha diversity of plants, but not of arthropods. Agricultural lands had a positive relationship with plants and herbivores, but a negative relationship with predators. Pastures positively influenced the diversity of plants and arthropods. In addition, forest cover seemed to influence changes in plant species composition and species turnover of herbivore communities among cornfields. The dominant plant species varied among fields, resulting in high differentiation of plant communities. Predator communities also exhibited high turnover among cornfields, but differences in composition arose mainly among rare species. The crop system evaluated in this study represents a widespread situation in the tropics, therefore, our results can be of broad significance. Our findings suggest that traditional agriculture may not homogenize biological communities, but instead could maintain the regional pool of species through high beta diversity. PMID:26197473

  12. Habitat Heterogeneity Affects Plant and Arthropod Species Diversity and Turnover in Traditional Cornfields.

    PubMed

    Martínez, Eliana; Rös, Matthias; Bonilla, María Argenis; Dirzo, Rodolfo

    2015-01-01

    The expansion of the agricultural frontier by the clearing of remnant forests has led to human-dominated landscape mosaics. Previous studies have evaluated the effect of these landscape mosaics on arthropod diversity at local spatial scales in temperate and tropical regions, but little is known about fragmentation effects in crop systems, such as the complex tropical traditional crop systems that maintain a high diversity of weeds and arthropods in low-Andean regions. To understand the factors that influence patterns of diversity in human-dominated landscapes, we investigate the effect of land use types on plant and arthropod diversity in traditionally managed cornfields, via surveys of plants and arthropods in twelve traditional cornfields in the Colombian Andes. We estimated alpha and beta diversity to analyze changes in diversity related to land uses within a radius of 100 m to 1 km around each cornfield. We observed that forests influenced alpha diversity of plants, but not of arthropods. Agricultural lands had a positive relationship with plants and herbivores, but a negative relationship with predators. Pastures positively influenced the diversity of plants and arthropods. In addition, forest cover seemed to influence changes in plant species composition and species turnover of herbivore communities among cornfields. The dominant plant species varied among fields, resulting in high differentiation of plant communities. Predator communities also exhibited high turnover among cornfields, but differences in composition arose mainly among rare species. The crop system evaluated in this study represents a widespread situation in the tropics, therefore, our results can be of broad significance. Our findings suggest that traditional agriculture may not homogenize biological communities, but instead could maintain the regional pool of species through high beta diversity.

  13. [The effect of sodium fluoride on selected biochemical markers of bone turnover in ovariectomized rats].

    PubMed

    Bohatyrewicz, A

    1998-10-01

    The aim of the study was to investigate the effect of fluoride on selected biochemical markers of bone remodelling in young growing rats and after ovariectomy performed on 12-weeks-old female Wistar rats. Seventy 6-weeks-old female Wistar rats were randomized into seven groups. The first baseline control group was sacrificed before the beginning of the experiment. Two groups served as controls receiving distilled water and the other groups received fluoridated water at different doses (two received 8 and two received 60 mgF-/l). 30 rats (ten from each group) were sacrificed after 6 weeks. Serum was then collected for measurement of fluoride concentration, serum total alkaline phosphatase activity (ALP) and concentration of telopeptide of rat type I collagen (ICTP). Last three groups (ten rats each) were ovariectomized and received than only distilled water to drink. After following six weeks all rats were sacrificed. After six weeks of experiment the group receiving 8 mg F-/l showed the lowest ICTP values and the smallest decrease of serum ALP activity compared to the baseline control group. The rats with higher plasma fluoride concentrations after ovariectomy demonstrated lower ICTP concentrations and higher ALP activity than animals with lower fluoride concentrations. PMID:10101440

  14. Relationship among dietary estimates of net endogenous acid production, bone mineral density and biochemical markers of bone turnover in an Iranian general population.

    PubMed

    Rahbar, Alireza; Larijani, Bagher; Nabipour, Iraj; Mohamadi, Mohamad Mehdi; Mirzaee, Kamran; Amiri, Zahra

    2009-11-01

    Chronic, low-grade metabolic acidosis due to Western diets may be a risk factor for osteoporosis. The severity can be determined in part by net endogenous acid production (NEAP). In a population-based study, a total of 1028 healthy men and women aged 20-72 years were evaluated for dietary intakes and NEAP estimates with a validated food frequency questionnaire. Dual-energy X-ray absorptiometry (DXA) was used to determine BMD of the lumbar spine (L2-L4), distal third of radius, and proximal femur. Serum CrossLaps, degradation products of the C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific ELISA methods. Lower estimates of energy-adjusted rates of NEAP were associated with greater femoral neck BMD (p=0.01) in premenopausal women and with greater BMDs at the distal radius (p=0.001) and lumbar spine (p=0.04) in postmenopausal women. Compared with women in the highest quartile of the estimates of the energy-adjusted rates of NEAP, pre- and postmenopausal women in the lowest quartile had significantly greater means of osteocalcin [9.12 (SD+/-1.62) vs. 5.24 (SD+/-1.41) ng/ml, p=0.02 and 11.74 (SD+/-1.69) vs. 7.79 (SD+/-2.63) ng/ml, p=0.002, respectively]. Analysis by quartiles of the estimates of energy-adjusted rates of NEAP did not reveal a relationship between BMD and bone turnover markers in men. In conclusion, we found that a high energy-adjusted rate of NEAP was associated with a significantly lower BMD in women but not in men and the energy-adjusted rate of NEAP had a negative relationship with bone formation.

  15. FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC

    PubMed Central

    Merolla, Francesco; Poser, Ina; Visconti, Roberta; Ilardi, Gennaro; Paladino, Simona; Inuzuka, Hiroyuki; Guggino, Gianluca; Monaco, Roberto; Colecchia, David; Monaco, Guglielmo; Cerrato, Aniello; Chiariello, Mario; Denning, Krista; Claudio, Pier Paolo; Staibano, Stefania; Celetti, Angela

    2015-01-01

    CCDC6 gene product is a pro-apoptotic protein substrate of ATM, whose loss or inactivation enhances tumour progression. In primary tumours, the impaired function of CCDC6 protein has been ascribed to CCDC6 rearrangements and to somatic mutations in several neoplasia. Recently, low levels of CCDC6 protein, in NSCLC, have been correlated with tumor prognosis. However, the mechanisms responsible for the variable levels of CCDC6 in primary tumors have not been described yet. We show that CCDC6 turnover is regulated in a cell cycle dependent manner. CCDC6 undergoes a cyclic variation in the phosphorylated status and in protein levels that peak at G2 and decrease in mitosis. The reduced stability of CCDC6 in the M phase is dependent on mitotic kinases and on degron motifs that are present in CCDC6 and direct the recruitment of CCDC6 to the FBXW7 E3 Ubl. The de-ubiquitinase enzyme USP7 appears responsible of the fine tuning of the CCDC6 stability, affecting cells behaviour and drug response. Thus, we propose that the amount of CCDC6 protein in primary tumors, as reported in lung, may depend on the impairment of the CCDC6 turnover due to altered protein-protein interaction and post-translational modifications and may be critical in optimizing personalized therapy. PMID:25885523

  16. FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC.

    PubMed

    Morra, Francesco; Luise, Chiara; Merolla, Francesco; Poser, Ina; Visconti, Roberta; Ilardi, Gennaro; Paladino, Simona; Inuzuka, Hiroyuki; Guggino, Gianluca; Monaco, Roberto; Colecchia, David; Monaco, Guglielmo; Cerrato, Aniello; Chiariello, Mario; Denning, Krista; Claudio, Pier Paolo; Staibano, Stefania; Celetti, Angela

    2015-05-20

    CCDC6 gene product is a pro-apoptotic protein substrate of ATM, whose loss or inactivation enhances tumour progression. In primary tumours, the impaired function of CCDC6 protein has been ascribed to CCDC6 rearrangements and to somatic mutations in several neoplasia. Recently, low levels of CCDC6 protein, in NSCLC, have been correlated with tumor prognosis. However, the mechanisms responsible for the variable levels of CCDC6 in primary tumors have not been described yet.We show that CCDC6 turnover is regulated in a cell cycle dependent manner. CCDC6 undergoes a cyclic variation in the phosphorylated status and in protein levels that peak at G2 and decrease in mitosis. The reduced stability of CCDC6 in the M phase is dependent on mitotic kinases and on degron motifs that are present in CCDC6 and direct the recruitment of CCDC6 to the FBXW7 E3 Ubl. The de-ubiquitinase enzyme USP7 appears responsible of the fine tuning of the CCDC6 stability, affecting cells behaviour and drug response.Thus, we propose that the amount of CCDC6 protein in primary tumors, as reported in lung, may depend on the impairment of the CCDC6 turnover due to altered protein-protein interaction and post-translational modifications and may be critical in optimizing personalized therapy.

  17. Effects of Glycemic Control on Bone Turnover in Older Mexican Americans with Type 2 Diabetes: Data from the Cameron County Hispanic Cohort in Texas

    NASA Technical Reports Server (NTRS)

    Rianon, N.; Smith, S. M.; Lee, M.; Musgrave, P.; Nader, S.; Khosla, S.; Ambrose, C.; McCormick, J.; Fisher-Hoch, S.

    2016-01-01

    High bone turnover, evidenced by high serum osteocalcin (OC) concentration, is indicated as risk of fracture in old age. However, low bone turnover has been reported in patients with type 2 diabetes (T2D) who also have high fracture risk. Poor glycemic control indicated by higher glycated hemoglobin levels (HbA1c) has been associated with lower serum OC in older Caucasian and Asian patients with T2D. There remains a gap in knowledge about effects of T2D on bone turnover status in Hispanic populations. We report bone turnover in association with glycemic control in 72 older (greater than or equal to 50 years) men (N=21) and women (N=51) from the Cameron County Hispanic Cohort (CCHC) in Texas. Prevalence of T2D is about 30 percent in this cohort who live in health disparity due to poor access to health care. Separate multivariable linear regression models were conducted to determine association between high/diabetic levels of HbA1c (less than 6.5 normal versus greater than or equal to 6.5 high) and serum OC after controlling for age, body mass index (BMI, greater than 30 obese versus less than 30 non-obese), visceral fat, femoral neck BMD and serum concentrations of creatinine, calcium, and vitamin D for men and women. Interaction effects were assessed while developing final multivariable model to identify factors that modify the association between HbA1c and OC. Subjects were 66 plus or minus 9 (mean plus or minus Standard Deviation) years for men and 67 plus or minus 8 years for women. HbA1c was 8.0 plus or minus 2.0 for men and 7.8 plus or minus 2.0 for women. There were no significant differences for BMI, femoral neck BMD, serum calcium or 25-hydroxyvitamin D concentrations between men and women. High HbA1c was significantly associated with lower OC levels in men in both age groups (mean difference in OC between high vs. low HbA1c [95 percent confidence interval] for older group (greater than or equal to 65 years) was minus 9.51 (minus 16.36 to minus 2.65) and

  18. Antecedents of Student Teachers' Affective Commitment to the Teaching Profession and Turnover Intention

    ERIC Educational Resources Information Center

    Christophersen, Knut-Andreas; Elstad, Eyvind; Solhaug, Trond; Turmo, Are

    2016-01-01

    Several European countries have experienced both a dearth of and reduction in the quality of applicants to teacher education study programmes. There is also significant leakage from these programmes. The rationale for this study therefore lies in the need to reduce teacher attrition. Research indicates that affective commitment to a profession is…

  19. The relation of the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene to peak bone mass and bone turnover rate among young healthy men.

    PubMed

    Välimäki, Ville-Valtteri; Piippo, Kirsi; Välimäki, Stiina; Löyttyniemi, Eliisa; Kontula, Kimmo; Välimäki, Matti J

    2005-12-01

    The genes coding for estrogen receptor-alpha (ER-alpha) and androgen receptors (AR) are potential candidates for the regulation of bone mass and turnover, which may contribute to both the achievement of peak bone mass and bone loss after completion of growth. The present study was aimed at elucidating the role of two restriction fragment lengths (XbaI and PvuII) polymorphisms of the ER gene and the CAG repeat polymorphism of the AR gene as determinants of peak bone mass in men; special attention was paid to the interaction between serum free estradiol (E2) levels and the XbaI and PvuII genotypes. A cross-sectional study, with data on lifestyle factors collected retrospectively, was performed in 234 young men, aged 18.3 to 20.6 years. Of the men, 184 were recruits of the Finnish Army and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content (BMC), density (BMD) and scan area were measured in the lumbar spine and upper femur by dual-energy X-ray absorptiometry (DXA). The bone turnover rate was assessed by measuring serum type I procollagen aminoterminal propeptide (PINP) and tartrate-resistant acid phosphatase 5b (TRACP5b) as well as urinary excretion of type I collagen aminoterminal telopeptide (NTX). After adjusting for age, height, weight, exercise, smoking, calcium and alcohol intake, BMC, scan area and BMD at all measurement sites were similar for the different XbaI and PvuII genotypes of the ER and independent of the number of the CAG repeats of the AR gene. No association was found between free E2 levels and bone parameters among any genotype group of the XbaI and PvuII polymorphisms. Except for urinary NTX, which showed a tendency to higher values for the xx (P=0.08) and pp (P=0.10) genotypes of the ER, bone turnover markers were not related to the genotypes studied. Our study does not support the view that the XbaI and PvuII polymorphisms of the ER gene and the CAG polymorphism of the AR

  20. [Factors affecting bone regeneration in Ilizarov callus distraction].

    PubMed

    Fink, B; Krieger, M; Schneider, T; Menkhaus, S; Fischer, J; Rüther, W

    1995-12-01

    We evaluated the X-rays of 36 patients who underwent 50 callus distractions. With the aid of a computerized digitalisation system for analogue films, the relative X-ray density of the distraction area was calculated for each X-ray. These relative X-ray densities were figured graphically for the duration of treatment for each patient. In the consolidation phase, the graph of each patient had a logarithmic relationship. The gradients of the logarithmic density curves were considered an indicator of the quantity of new bone formation. These gradients were correlated to the following clinical parameters: age of the patient, beginning of distraction after corticotomy, average speed of distraction, average weight bearing during the distraction and consolidation phase, location of corticotomy (distal femur versus proximal tibia) and diclofenac medication. Except for the location of the corticotomy and diclofenac, all parameters had an influence on osteoneogenesis by callus distraction. The parameters affecting new bone formation the most were the age of the patient and weight bearing. Patients aged under 18 years (p = 0.005), beginning of distraction later than 8 days (p = 0.109), an average distraction speed below 1 mm/day (p = 0.079), and average weight bearing of more than 30 kg (p = 0.068 for the distraction phase and p = 0.089 for the consolidation phase) showed a quantitatively higher rate of new bone formation by callus distraction than the patients in the other groups. Patients with a shorter leg due to poliomyelitis and one patient with an amniotic leg tie showed a slower increase in X-ray density graphs than the other patients. PMID:8584945

  1. Bone development in black ducks as affected by dietary toxaphene

    USGS Publications Warehouse

    Mehrle, P.M.; Finley, M.T.; Ludke, J.L.; Mayer, F.L.; Kaiser, T.E.

    1979-01-01

    Black ducks, Anas rubripes, were exposed to dietary toxaphene concentrations of 0, 10, or 50 μg/g of food for 90 days prior to laying and through the reproductive season. Toxaphene did not affect reproduction or survival, but reduced growth and impaired backbone development in ducklings. Collagen, the organic matrix of bone, was decreased significantly in cervical vertebrae of ducklings fed 50 μg/g, and calcium conentrations increased in vertebrae of ducklings fed 10 or 50 μg/g. The effects of toxaphene were observed only in female ducklings. In contrast to effects on vertebrae, toxaphene exposure did not alter tibia development. Toxaphene residues in carcasses of these ducklings averaged slightly less than the dietary levels.

  2. Increased nitrogen deposition did not affect the composition and turnover of plant and microbial biomarkers in forest soil density fractions

    NASA Astrophysics Data System (ADS)

    Griepentrog, Marco; Bodé, Samuel; Boeckx, Pascal; Hagedorn, Frank; Wiesenberg, Guido L. B.; Schmidt, Michael W. I.

    2013-04-01

    Increased atmospheric nitrogen (N) deposition and elevated CO2 concentrations affect many forests and their ecosystem functions, including organic matter cycling in soils, the largest carbon pool of terrestrial ecosystems. However, it is still not clear how, and what the underlying mechanisms are. Specific molecules of plant and microbial origin (biomarkers) might respond differently to N deposition, depending on their internal N content. Microbial cell-wall-constituents with high-N content like amino sugars are reliable biomarkers to distinguish between fungal- and bacterial-derived organic residues. Individual lipids are plant-specific biomarkers that lack N in their molecular structure. Here, we tested the effects of elevated CO2 and increased N deposition on the dynamics of plant and microbial biomarkers by studying their composition and turnover in forest soil density fractions. Furthermore, we tested the hypothesis that these biomarkers respond differently to increased N deposition, depending on their internal N content. We used soil samples from a 4-year elevated CO2 and N deposition experiment in model forest ecosystems (open-top chambers), that were fumigated with ambient and 13C-depleted CO2 and treated with two levels of 15N-labeled fertilizer. Bulk soil was separated into free light fraction, occluded light fraction and heavy fraction by density fractionation and ultrasonic dispersion. The heavy fraction was further particle-size fractionated with 20 μm as a cut-off. We determined carbon and N concentrations and their isotopic compositions (δ13C, δ15N) within bulk soil and density fractions. Therein, we extracted and quantified individual amino sugars and lipids and conducted compound-specific stable-isotope-analysis using GC- and LC-IRMS. Results show that amino sugars were mainly stabilized in association with soil minerals. Especially bacterial amino sugars were preferentially associated with soil minerals, exemplified by a consistent decrease

  3. Effect of the Medicinal Mushroom, Grifola gargal (Agaricomycetes), on Bone Turnover Markers and Serum Lipids in Middle-Aged and Elderly Japanese Women.

    PubMed

    Harada, Etsuko; Morizono, Toshihiro; Sumiya, Toshimitsu; Kawagishi, Hirokazu

    2016-01-01

    A clinical study was performed to examine the effect of the edible mushroom, Grifola gargal, on bone turnover markers and serum lipids in middle-aged and elderly Japanese women. Postmenopausal women aged 51-73 years (mean age, 61 years) received daily oral administration of 5 g G. gargal fruiting bodies (hot air-dried and powdered; G. gargal powder [GGP]). Serum levels of bone alkaline phosphatase (BAP) and lipids and urinary deoxypyridinoline (DPD) levels were measured before and 2 weeks after the start of GGP treatment. As a result, urinary DPD bone resorption marker levels in women treated with GGP decreased significantly. Serum levels of the BAP bone formation marker also tended to increase, but the difference was not significant. By contrast, the atherogenic index decreased and the high-density lipoprotein (HDL) ratio increased significantly. However, there were no statistically significant differences in serum lipids of total cholesterol, HDL cholesterol, and low-density lipoprotein cholesterol. In addition, this study demonstrated for the first time that G. gargal is safe for human consumption. PMID:27279439

  4. Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicor...

  5. Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review.

    PubMed

    Konstantinidis, Ioannis; Papageorgiou, Spyridon N; Kyrgidis, Athanassios; Tzellos, Thrasivoulos-George; Kouvelas, Dimitrios

    2013-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review. PMID:23016823

  6. Comparison of the effects of cholecalciferol and calcitriol on calcium metabolism and bone turnover in Chinese postmenopausal women with vitamin D insufficiency

    PubMed Central

    Zhang, Hao; Huang, Qi-ren; Gu, Jie-mei; Hu, Wei-wei; Liu, Yu-juan; Hu, Yun-qiu; Zhang, Zhen-lin

    2012-01-01

    Aim: To compare the effects of cholecalciferol (800 IU/d) and calcitriol (0.25 μg/d) on calcium metabolism and bone turnover in Chinese postmenopausal women with vitamin D insufficiency. Methods: One hundred Chinese postmenopausal women aged 63.8±7.0 years and with serum 25-hydroxyvitamin D [25(OH)D] concentration <30 ng/mL were recruited. The subjects were divided into 2 groups based on the age and serum 25(OH)D concentration: 50 subjects (group A) received cholecalciferol (800 IU/d), and 50 subjects (group B) received calcitriol (0.25 μg/d) for 3 months. In addition, all the subjects received Caltrate D (calcium plus 125 IU cholecalciferol) daily in the form of one pill. The markers of calcium metabolism and bone turnover, including the serum levels of calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, 25(OH)D and β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX), were measured before and after the intervention. Results: After the 3-month intervention, the serum 25(OH)D concentration in group A was significantly increased from 16.01±5.0 to 20.02±4.5 ng/mL, while that in group B had no significant change. The serum calcium levels in both the groups were significantly increased (group A: from 2.36±0.1 to 2.45±0.1 mmol/L; group B: from 2.36±0.1 to 2.44±0.1 mmol/L). The levels of serum intact parathyroid hormone in both the groups were significantly decreased (group A: from 48.56±12.8 to 39.59±12.6 pg/mL; group B: from 53.67±20.0 to 40.32±15.4 pg/mL). The serum levels of β-CTX in both the groups were also significantly decreased (group A: from 373.93±135.3 to 325.04±149.0 ng/L; group B: from 431.00±137.1 to 371.74±185.0 ng/L). Conclusion: We concluded that both cholecalciferol (800 IU/d) and calcitriol (0.25 μg/d) plus Caltrate D modifies the serum calcium and bone turnover markers in Chinese postmenopausal women with vitamin D insufficiency. In addition, cholecalciferol (800 IU/d) significantly

  7. The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

    PubMed

    Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

    2014-06-01

    The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p < 0.05) (RT: 64 ± 14 to 80 ± 17 kg; RT+DP: 72 ± 23 to 91 ± 20 kg) and lower (p < 0.05) (RT: 69 ± 20 to 87 ± 28 kg; RT+DP: 78 ± 19 to 100 ± 21 kg) body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05) (4.55 ± 1.57 to 4.04 ± 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 ± 2.75 to 4.27 ± 2.03 U/L). Changes in BAP and CRP were not observed. RT was effective for improving biochemical markers of bone turnover and muscular strength in BCS. A longer and higher intensity intervention may be needed to reveal the true effects of RT and DP on body composition and biochemical markers of inflammation.

  8. Osteoblast-Specific Deletion of Pkd2 Leads to Low-Turnover Osteopenia and Reduced Bone Marrow Adiposity

    PubMed Central

    Xiao, Zhousheng; Cao, Li; Liang, Yingjuan; Huang, Jinsong; Stern, Amber Rath; Dallas, Mark; Johnson, Mark; Quarles, Leigh Darryl

    2014-01-01

    Polycystin-1 (Pkd1) interacts with polycystin-2 (Pkd2) to form an interdependent signaling complex. Selective deletion of Pkd1 in the osteoblast lineage reciprocally regulates osteoblastogenesis and adipogenesis. The role of Pkd2 in skeletal development has not been defined. To this end, we conditionally inactivated Pkd2 in mature osteoblasts by crossing Osteocalcin (Oc)-Cre;Pkd2+/null mice with floxed Pkd2 (Pkd2flox/flox) mice. Oc-Cre;Pkd2flox/null (Pkd2Oc-cKO) mice exhibited decreased bone mineral density, trabecular bone volume, cortical thickness, mineral apposition rate and impaired biomechanical properties of bone. Pkd2 deficiency resulted in diminished Runt-related transcription factor 2 (Runx2) expressions in bone and impaired osteoblastic differentiation ex vivo. Expression of osteoblast-related genes, including, Osteocalcin, Osteopontin, Bone sialoprotein (Bsp), Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex), Dentin matrix protein 1 (Dmp1), Sclerostin (Sost), and Fibroblast growth factor 23 (FGF23) were reduced proportionate to the reduction of Pkd2 gene dose in bone of Oc-Cre;Pkd2flox/+ and Oc-Cre;Pkd2flox/null mice. Loss of Pkd2 also resulted in diminished peroxisome proliferator-activated receptor γ (PPARγ) expression and reduced bone marrow fat in vivo and reduced adipogenesis in osteoblast culture ex vivo. Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP), reciprocally acting as co-activators and co-repressors of Runx2 and PPARγ, were decreased in bone of Oc-Cre;Pkd2flox/null mice. Thus, Pkd1 and Pkd2 have coordinate effects on osteoblast differentiation and opposite effects on adipogenesis, suggesting that Pkd1 and Pkd2 signaling pathways can have independent effects on mesenchymal lineage commitment in bone. PMID:25464512

  9. Does Orthodontic Treatment Affect the Alveolar Bone Density?

    PubMed

    Yu, Jian-Hong; Huang, Heng-Li; Liu, Chien-Feng; Wu, Jay; Li, Yu-Fen; Tsai, Ming-Tzu; Hsu, Jui-Ting

    2016-03-01

    Few studies involving human participants have been conducted to investigate the effect of orthodontic treatment on alveolar bone density around the teeth. Our previous study revealed that patients who received 6 months of active orthodontic treatment exhibited an ∼24% decrease in alveolar bone density around the teeth. However, after an extensive retention period following orthodontic treatment, whether the bone density around the teeth can recover to its original state from before the treatment remains unclear, thus warranting further investigation.The purpose of this study was to assess the bone density changes around the teeth before, during, and after orthodontic treatment.Dental cone-beam computed tomography (CBCT) was used to measure the changes in bone density around 6 teeth in the anterior maxilla (maxilla central incisors, lateral incisors, and canines) of 8 patients before and after orthodontic treatment. Each patient underwent 3 dental CBCT scans: before treatment (T0); at the end of 7 months of active orthodontic treatment (T1); after several months (20-22 months) of retention (T2). The Friedman test was applied to evaluate the changes in the alveolar bone density around the teeth according to the 3 dental CBCT scans.From T0 to T1, a significant reduction in bone density was observed around the teeth (23.36 ± 10.33%); by contrast, a significant increase was observed from T1 to T2 (31.81 ± 23.80%). From the perspective of the overall orthodontic treatment, comparing the T0 and T2 scans revealed that the bone density around the teeth was relatively constant (a reduction of only 0.75 ± 19.85%). The results of the statistical test also confirmed that the difference in bone density between T0 and T2 was nonsignificant.During orthodontic tooth movement, the alveolar bone density around the teeth was reduced. However, after a period of bone recovery, the reduced bone density recovered to its previous state from before the orthodontic treatment

  10. Does Orthodontic Treatment Affect the Alveolar Bone Density?

    PubMed Central

    Yu, Jian-Hong; Huang, Heng-Li; Liu, Chien-Feng; Wu, Jay; Li, Yu-Fen; Tsai, Ming-Tzu; Hsu, Jui-Ting

    2016-01-01

    Abstract Few studies involving human participants have been conducted to investigate the effect of orthodontic treatment on alveolar bone density around the teeth. Our previous study revealed that patients who received 6 months of active orthodontic treatment exhibited an ∼24% decrease in alveolar bone density around the teeth. However, after an extensive retention period following orthodontic treatment, whether the bone density around the teeth can recover to its original state from before the treatment remains unclear, thus warranting further investigation. The purpose of this study was to assess the bone density changes around the teeth before, during, and after orthodontic treatment. Dental cone-beam computed tomography (CBCT) was used to measure the changes in bone density around 6 teeth in the anterior maxilla (maxilla central incisors, lateral incisors, and canines) of 8 patients before and after orthodontic treatment. Each patient underwent 3 dental CBCT scans: before treatment (T0); at the end of 7 months of active orthodontic treatment (T1); after several months (20–22 months) of retention (T2). The Friedman test was applied to evaluate the changes in the alveolar bone density around the teeth according to the 3 dental CBCT scans. From T0 to T1, a significant reduction in bone density was observed around the teeth (23.36 ± 10.33%); by contrast, a significant increase was observed from T1 to T2 (31.81 ± 23.80%). From the perspective of the overall orthodontic treatment, comparing the T0 and T2 scans revealed that the bone density around the teeth was relatively constant (a reduction of only 0.75 ± 19.85%). The results of the statistical test also confirmed that the difference in bone density between T0 and T2 was nonsignificant. During orthodontic tooth movement, the alveolar bone density around the teeth was reduced. However, after a period of bone recovery, the reduced bone density recovered to its previous state from before the

  11. Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

    PubMed Central

    de la Piedra, C; Alcaraz, A; Bellmunt, J; Meseguer, C; Gómez-Caamano, A; Ribal, M J; Vázquez, F; Anido, U; Samper, P; Esteban, E; Álvarez-Ossorio, J L; Lara, P C; San José, L A; Contreras, J A; del Alba, A G; González-Gragera, B; Tabernero, A J; González-Enguita, C; Fernández, J M; García-Escudero, A; Gómez-Veiga, F; Méndez, M J; Segarra, J; Virizuela, J A; Carles, J; Lassa, A; Calderero, V; Constela, M; Delgado, D; Mañas, A; Murias, A; Reynes, G; Rodriguez, B; Rubio, G; Sánchez, E; Unda, M; Solsona, E; Martínez-Javaloyas, J M; Comet-Batlle, J; Quicios, C; Martín-Fernández, M; Mahillo-Fernández, I; Morote, J

    2013-01-01

    Background: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important. PMID:23722472

  12. Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures.

    PubMed

    Shigdel, Rajesh; Osima, Marit; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Zebaze, Roger; Bjørnerem, Åshild

    2015-12-01

    Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to

  13. Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures.

    PubMed

    Shigdel, Rajesh; Osima, Marit; Ahmed, Luai A; Joakimsen, Ragnar M; Eriksen, Erik F; Zebaze, Roger; Bjørnerem, Åshild

    2015-12-01

    Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to

  14. Pyridoxine deficiency affects biomechanical properties of chick tibial bone

    NASA Technical Reports Server (NTRS)

    Masse, P. G.; Rimnac, C. M.; Yamauchi, M.; Coburn, S. P.; Rucker, R. B.; Howell, D. S.; Boskey, A. L.

    1996-01-01

    The mechanical integrity of bone is dependent on the bone matrix, which is believed to account for the plastic deformation of the tissue, and the mineral, which is believed to account for the elastic deformation. The validity of this model is shown in this study based on analysis of the bones of vitamin B6-deficient and vitamin B6-replete chick bones. In this model, when B6-deficient and control animals are compared, vitamin B6 deficiency has no effect on the mineral content or composition of cortical bone as measured by ash weight (63 +/- 6 vs. 58 +/- 3); mineral to matrix ratio of the FTIR spectra (4.2 +/- 0.6 vs. 4.5 +/- 0.2), line-broadening analyses of the X-ray diffraction 002 peak (beta 002 = 0.50 +/- 0.1 vs. 0.49 +/- 0.01), or other features of the infrared spectra. In contrast, collagen was significantly more extractable from vitamin B6-deficient chick bones (20 +/- 2% of total hydroxyproline extracted vs. 10 +/- 3% p < or = 0.001). The B6-deficient bones also contained an increased amount of the reducible cross-links DHLNL, dehydro-dihydroxylysinonorleucine, (1.03 +/- 0.07 vs. 0.84 +/- 0.13 p < or = 0.001); and a nonsignificant increase in HLNL, dehydro-hydroxylysinonorleucine, (0.51 +/- 0.03 vs. 0.43 +/- 0.03, p < or = 0.10). There were no significant changes in bone length, bone diameter, or area moment of inertia. In four-point bending, no significant changes in elastic modulus, stiffness, offset yield deflection, or fracture deflection were detected. However, fracture load in the B6-deficient animals was decreased from 203 +/- 35 MPa to 151 +/- 23 MPa, p < or = 0.01, and offset yield load was decreased from 165 +/- 9 MPa to 125 +/- 14 MPa, p < or = 0.05. Since earlier histomorphometric studies had demonstrated that the B6-deficient bones were osteopenic, these data suggest that although proper cortical bone mineralization occurred, the alterations of the collagen resulted in changes to bone mechanical performance.

  15. Cochlear otosclerosis: does bone formation affect cochlear implant surgery?

    PubMed

    Fayad, J; Moloy, P; Linthicum, F H

    1990-05-01

    This study aimed to demonstrate that new bone formation in the scala tympani of patients deaf from otosclerosis does not preclude cochlear implant surgery. In seven temporal bones from patients with otosclerosis, we measured the extent of new bone from the round window to the distal part of the new growth. We compared results to surgical data on the extent of drilling and depth and ease of placement of the electrode in 20 patients deaf from otosclerosis. We also examined clinical performance and voltage requirements for long-term implant use in patients with and patients without ossification of the scala tympani. Findings in our limited sample of patients and bones show that obstruction of the basal turn, which occurs in some otosclerotic patients, does not preclude implant surgery. The dynamic range in the studied sample was relatively stable long-term and clinical performance did not differ between groups with and without an ossified scala tympani. PMID:2188511

  16. Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors.

    PubMed

    Laaksonen, Marika; Kärkkäinen, Merja; Outila, Terhi; Vanninen, Tarja; Ray, Carola; Lamberg-Allardt, Christel

    2002-01-01

    Bone mineral density (BMD) is regulated by genetic and environmental factors. Sixty percent to 80% of bone mass is suggested to be under polygenetic control, but the role of individual genes seems to be modest. Several studies have indicated that the vitamin D receptor ( VDR) gene has a role in the regulation of BMD and bone metabolism, but the results are very controversial. We studied the associations between BsmI-polymorphism of the VDR gene and BMD and bone metabolism in 24 premenopausal (aged 22-45 years) and 69 postmenopausal (aged 48-65 years) Finnish women. The BMD of the lumbar spine and femoral neck and bone turnover markers were measured, and the intestinal calcium absorption was investigated, using a method based on the absorption of non-radioactive strontium. The genotype distribution was 16%, BB; 34.5%, Bb; and 49.5%, bb, which differs from the genotype distribution found in other Caucasian populations, but is similar to earlier Finnish reports. The winter value of 25-hydroxyvitamin-D (25-OH-D) was highest for the BB genotype in both age groups (analysis of covariance [ANCOVA]; premenopausal women P = 0.5, postmenopausal women P = 0.03, and for the groups combined P = 0.02). Lumbar spine BMD and intestinal strontium absorption were highest for the BB genotype in both age groups, but these results were nonsignificant. The markers of bone metabolism did not differ significantly between the VDR genotypes. The BB genotype had the best vitamin D status, which could explain the differences in calcium absorption between the genotypes. However, the conclusions of our study are limited because of the small number of subjects. PMID:12434167

  17. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.

    PubMed

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  18. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits

    PubMed Central

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  19. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

    PubMed

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping

    2014-01-01

    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  20. Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women a randomized dose-finding trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bic...

  1. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  2. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    PubMed

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. PMID:26944960

  3. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    PubMed

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects.

  4. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    PubMed Central

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  5. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    PubMed

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  6. Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized Controlled Trial Data.

    PubMed

    Bell, Katy Jl; Hayen, Andrew; Glasziou, Paul; Irwig, Les; Eastell, Richard; Harrison, Stephanie L; Black, Dennis M; Bauer, Douglas C

    2016-09-01

    We aimed to compare the clinical validity and the detectability of response of short-term changes in bone mineral density (BMD; hip and spine) and bone turnover markers (serum PINP and CTX) through secondary analysis of trial data. We analyzed data on 7765 women with osteoporosis randomized to 5-mg once-yearly infusions of zoledronic acid or placebo in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT; trial ran from 2002 to 2006) and the first extension trial (trial ran from 2006 to 2009). We assessed the clinical validity and detectability of response for 1-year measurements of the following monitoring tests: total hip and lumbar spine BMD, serum N-terminal propeptide of type I collagen (sPINP), and serum C-telopeptide of type I collagen (sCTX; 6-month measurement used). Clinical validity was assessed by examining prediction of clinical fracture in Cox models; detectability of response to treatment was assessed by the ratio of signal to noise, estimated from the distributions of change in zoledronic acid and placebo groups. Baseline measurements were available for 7683 women with hip BMD, 558 with spine BMD, 1246 with sPINP, and 517 women with sCTX. Hip BMD and sPINP ranked highly for prediction of clinical fracture, whereas sPINP and sCTX ranked highly for detectability of response to treatment. Serum PINP had the highest overall ranking. In conclusion, serum PINP is potentially useful in monitoring response to zoledronic acid. Further research is needed to evaluate the effects of monitoring PINP on treatment decisions and other clinically relevant outcomes. © 2016 American Society for Bone and Mineral Research. PMID:27027655

  7. Does aspiration of bones and joints affect results of later bone scanning

    SciTech Connect

    Canale, S.T.; Harkness, R.M.; Thomas, P.A.; Massie, J.D.

    1985-01-01

    To determine the effect, if any, of needle aspiration on /sup 99m/Tc bone scanning, three different areas of 15 dogs were first aspirated and then imaged with technetium bone scintigraphy. The hip joint was aspirated, the distal femoral metaphysis was drilled and aspirated, and the tibial periosteum was scraped with an 18- or 20-gauge needle. Varying amounts of trauma were inflicted to simulate varying difficulties at aspiration. /sup 99m/Tc bone scans were obtained from 5 h to 10 days later. There was no evidence of focal technetium uptake after any hip joint aspiration. This was consistent regardless of the amount of trauma inflicted or the time from aspiration to bone scanning. Metaphyseal cortical drilling and tibial periosteal scraping occasionally caused some focal uptake when scanning was delayed greater than 2 days. When osteomyelitis or pyarthrosis is clinically suspected, joint aspiration can be performed without fear of producing a false- positive bone scan.

  8. Interrelationships between tooth properties and biochemical bone turnover markers investigated on six-month-old pig model.

    PubMed

    Tymczyna, Barbara; Tatara, Marcin R; Krupski, Witold; Tymczyna-Sobotka, Monika; Bachanek, Teresa

    2013-01-01

    The aim of the study was to determine interrelationships between bone tissue metabolism indices and morphological, biomechanical and densitometric properties of hard dental tissues. First primary maxillary incisor from 6-month-old pigs (N=27) was evaluated in terms of weight and length. Mean volumetric tooth mineral density, total tooth volume, enamel total volume, enamel volumetric mineral density, dentine total volume and dentine volumetric mineral density were estimated with the use of quantitative computed tomography and micro computed tomography techniques. Tooth mineral density and tooth mineral content were evaluated with the use of dual-energy X-ray absorptiometry. Microhardness of enamel was measured using Vicker's test. Evaluations of total calcium, ionized calcium, magnesium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type-I collagen (CTX), insulin-like growth factor-1, growth hormone and parathyroid hormone were performed in plasma and serum samples. Pearson's correlation coefficients were determined between all the investigated variables, and P<0.05 was considered as statistically significant. The obtained results have shown mainly mutual dependences between biochemical indicators of bone metabolism. Evaluation of CTX concentration in serum of pigs has shown the highest predictive value in relation to morphological, densitometric and biomechanical properties of teeth. PMID:23076035

  9. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  10. How the Timing of Climate Change Policy Affects Infrastructure Turnover in the Electricity Sector: Engineering, Economic and Policy Considerations

    NASA Astrophysics Data System (ADS)

    Izard, Catherine Finlay

    The electricity sector is responsible for producing 35% of US greenhouse gas (GHG) emissions. Estimates suggest that ideally, the electricity sector would be responsible for approximately 85% of emissions abatement associated with climate polices such as America's Clean Energy and Security Act (ACES). This is equivalent to ˜50% cumulative emissions reductions below projected cumulative business-as-usual (BAU) emissions. Achieving these levels of emissions reductions will require dramatic changes in the US electricity generating infrastructure: almost all of the fossil-generation fleet will need to be replaced with low-carbon sources and society is likely to have to maintain a high build rate of new capacity for decades. Unfortunately, the inertia in the electricity sector means that there may be physical constraints to the rate at which new electricity generating capacity can be built. Because the build rate of new electricity generating capacity may be limited, the timing of regulation is critical---the longer the U.S. waits to start reducing GHG emissions, the faster the turnover in the electricity sector must occur in order to meet the same target. There is a real, and thus far unexplored, possibility that the U.S. could delay climate change policy implementation for long enough that it becomes infeasible to attain the necessary rate of turnover in the electricity sector. This dissertation investigates the relationship between climate policy timing and infrastructure turnover in the electricity sector. The goal of the dissertation is to answer the question: How long can we wait before constraints on infrastructure turnover in the electricity sector make achieving our climate goals impossible? Using the Infrastructure Flow Assessment Model, which was developed in this work, this dissertation shows that delaying climate change policy increases average retirements rates by 200-400%, increases average construction rates by 25-85% and increases maximum construction

  11. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

    PubMed

    Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2016-10-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

  12. Protein turnover and cellular stress in mildly and severely affected muscles from patients with limb girdle muscular dystrophy type 2I.

    PubMed

    Hauerslev, Simon; Sveen, Marie L; Vissing, John; Krag, Thomas O

    2013-01-01

    Patients with Limb girdle muscular dystrophy type 2I (LGMD2I) are characterized by progressive muscle weakness and wasting primarily in the proximal muscles, while distal muscles often are spared. Our aim was to investigate if wasting could be caused by impaired regeneration in the proximal compared to distal muscles. Biopsies were simultaneously obtained from proximal and distal muscles of the same patients with LGMD2I (n = 4) and healthy subjects (n = 4). The level of past muscle regeneration was evaluated by counting internally nucleated fibers and determining actively regenerating fibers by using the developmental markers embryonic myosin heavy chain (eMHC) and neural cell adhesion molecule (NCAM) and also assessing satellite cell activation status by myogenin positivity. Severe muscle histopathology was occasionally observed in the proximal muscles of patients with LGMD2I whereas distal muscles were always relatively spared. No difference was found in the regeneration markers internally nucleated fibers, actively regenerating fibers or activation status of satellite cells between proximal and distal muscles. Protein turnover, both synthesis and breakdown, as well as cellular stress were highly increased in severely affected muscles compared to mildly affected muscles. Our results indicate that alterations in the protein turnover and myostatin levels could progressively impair the muscle mass maintenance and/or regeneration resulting in gradual muscular atrophy.

  13. Healing following implantation of periodontitis affected roots into bone tissue.

    PubMed

    Karring, T; Nyman, S; Lindhe, J

    1980-04-01

    The aim of the present experiment was to study whether new connective tissue attachment can occur to root surfaces which have been exposed to the oral environment and subsequently implanted into bone tissue. Twelve teeth in three beagle dogs were subjected to progressive periodontal breakdown to half the root length by placing cotton floss ligatures around the neck of the teeth. Following crown resection and root hemisection, the teeth were root filled and the roots thoroughly scaled and planed. Each root was extracted and implanted into bone cavities prepared in edentolous areas of the jaws in such a way that epithelial migration into the wound and bacterial infection were prevented during healing. Root implantation and sacrifice of the animals were scheduled to allow for observation periods of 1, 2 and 3 months. The results demonstrated that new connective tissue attachment did not occur to root surfaces which had been exposed to the oral environment, but healing was characterized by repair phenomena, i.e. mainly root resorption and ankylosis. In those areas of the roots where periodontal ligament tissue was preserved following tooth extraction, a functionally oriented attachment apparatus was reformed. The results indicate that in addition to apical migration of junctional epithelium and regrowth of subgingival plaque, the type of cells which repopulate the wound area may jeopardize new connective tissue attachment.

  14. Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial

    PubMed Central

    2012-01-01

    Background There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks’ daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Methods Healthy adults aged 19–48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). Results S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. Conclusions Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. Trial Registration Clinical

  15. Cold-batter mincing of hot-boned and crust-freezing air-chilled turkey breast improved meat turnover time and product quality.

    PubMed

    Medellin-Lopez, M; Sansawat, T; Strasburg, G; Marks, B P; Kang, I

    2014-03-01

    The purpose of this research was to evaluate the combined effects of turkey hot-boning and cold-batter mincing technology on acceleration of meat turnover and meat quality improvement. For each of 3 replications, 15 turkeys were slaughtered and eviscerated. Three of the eviscerated carcasses were randomly assigned to water-immersion chilling for chill-boning (CB) and the remaining were immediately hot-boned (HB), half of which were used without chilling whereas the remaining were subjected to crust-freezing air chilling (CFAC) in an air-freezing room (1.0 m/s, -12°C) with/without 1/4; sectioning (HB-1/4;CFAC, HB-CFAC). As a result, CB and HB breasts were minced using 1 of 5 treatments: (1) CB and traditional mincing (CB-T), (2) HB and mincing with no chilling (HB-NC), (3) HB and mincing with CO2 (HB-CO2), (4) HB and mincing after CFAC (HB-CFAC), and (5) HB and mincing after quarter sectioning and CFAC (HB-1/4;CFAC). Traditional water-immersion chilling took an average of 5.5 h to reduce the breast temperature to 4°C, whereas HB-CFAC and HB-1/4;CFAC took 1.5 and 1 h, respectively. The breast of HB-CFAC and HB-1/4;CFAC showed significantly higher pH (6.0-6.1), higher fragmentation index (196-198), and lower R-value (1.0-1.1; P < 0.05) than those of the CB controls. No significant differences (P > 0.05) in sarcomere length were seen between CB-T and HB-CFAC filets regardless of quarter sectioning. When muscle was minced, the batter pH (5.9) of CB-T was significantly lower (P < 0.05) than those (6.1-6.3) of HB-NC, HB-CO2, and HB-1/4;CFAC, with the intermediate pH (6.0) seen for the HB-CFAC. When meat batters were cooked, higher cooking yield (90 - 91%; P < 0.05) was found in HB-CFAC, HB-1/4;CFAC, and HB-CO2, followed by HB-NC (90%) and finally CB-T (86%). Stress values (47-51 kPa) of HB-CFAC gels were significantly higher (P < 0.05) than those of CB-T (30 kPa) and HB-NC (36 kPa). A similar trend was found in strain values.

  16. Commitment Profiles and Employee Turnover

    ERIC Educational Resources Information Center

    Stanley, Laura; Vandenberghe, Christian; Vandenberg, Robert; Bentein, Kathleen

    2013-01-01

    We examined how affective (AC), normative (NC), perceived sacrifice (PS), and few alternatives (FA) commitments combine to form profiles and determine turnover intention and turnover. We theorized that three mechanisms account for how profiles operate, i.e., the degree to which membership is internally regulated, the perceived desirability and…

  17. Spatial pattern formation of microbes at the soil microscale affect soil C and N turnover in an individual-based microbial community model

    NASA Astrophysics Data System (ADS)

    Kaiser, Christina; Evans, Sarah; Dieckmann, Ulf; Widder, Stefanie

    2016-04-01

    At the μm-scale, soil is a highly structured and complex environment, both in physical as well as in biological terms, characterized by non-linear interactions between microbes, substrates and minerals. As known from mathematics and theoretical ecology, spatial structure significantly affects the system's behaviour by enabling synergistic dynamics, facilitating diversity, and leading to emergent phenomena such as self-organisation and self-regulation. Such phenomena, however, are rarely considered when investigating mechanisms of microbial soil organic matter turnover. Soil organic matter is the largest terrestrial reservoir for organic carbon (C) and nitrogen (N) and plays a pivotal role in global biogeochemical cycles. Still, the underlying mechanisms of microbial soil organic matter buildup and turnover remain elusive. We explored mechanisms of microbial soil organic matter turnover using an individual-based, stoichiometrically and spatially explicit computer model, which simulates the microbial de-composer system at the soil microscale (i.e. on a grid of 100 x 100 soil microsites). Soil organic matter dynamics in our model emerge as the result of interactions among individual microbes with certain functional traits (f.e. enzyme production rates, growth rates, cell stoichiometry) at the microscale. By degrading complex substrates, and releasing labile substances microbes in our model continusly shape their environment, which in turn feeds back to spatiotemporal dynamics of the microbial community. In order to test the effect of microbial functional traits and organic matter input rate on soil organic matter turnover and C and N storage, we ran the model into steady state using continuous inputs of fresh organic material. Surprisingly, certain parameter settings that induce resource limitation of microbes lead to regular spatial pattern formation (f.e. moving spiral waves) of microbes and substrate at the μm-scale at steady-state. The occurrence of these

  18. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

    PubMed Central

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  19. Turnover Time

    EPA Science Inventory

    Ecosystems contain energy and materials such as carbon, nitrogen, phosphorus, and water, and are open to their flow-through. Turnover time refers to the amount of time required for replacement by flow-through of the energy or substance of interest contained in the system, and is ...

  20. Pathophysiology of chronic kidney disease-mineral and bone disorder.

    PubMed

    Mac Way, Fabrice; Lessard, Myriam; Lafage-Proust, Marie-Hélène

    2012-12-01

    Chronic kidney disease (CKD) alters the metabolism of several minerals, thereby inducing bone lesions and vessel-wall calcifications that can cause functional impairments and excess mortality. The histological bone abnormalities seen in CKD, known as renal osteodystrophy, consist of alterations in the bone turnover rate, which may be increased (osteitis fibrosa [OF]) or severely decreased (adynamic bone disease [AD]); abnormal mineralization (osteomalacia [OM]), and bone loss. Secondary hyperparathyroidism is related to early phosphate accumulation (responsible for FGF23 overproduction by bone tissue), decreased calcitriol production by the kidneys, and hypocalcemia. Secondary hyperparathyroidism is associated with OF. Other factors that affect bone include acidosis, chronic inflammation, nutritional deficiencies, and iatrogenic complications.

  1. Pig slurry acidification and separation techniques affect soil N and C turnover and N2O emissions from solid, liquid and biochar fractions.

    PubMed

    Gómez-Muñoz, B; Case, S D C; Jensen, L S

    2016-03-01

    The combined effects of pig slurry acidification, subsequent separation techniques and biochar production from the solid fraction on N mineralisation and N2O and CO2 emissions in soil were investigated in an incubation experiment. Acidification of pig slurry increased N availability from the separated solid fractions in soil, but did not affect N2O and CO2 emissions. However acidification reduced soil N and C turnover from the liquid fraction. The use of more advanced separation techniques (flocculation and drainage > decanting centrifuge > screw press) increased N mineralisation from acidified solid fractions, but also increased N2O and CO2 emissions in soil amended with the liquid fraction. Finally, the biochar production from the solid fraction of pig slurry resulted in a very recalcitrant material, which reduced N and C mineralisation in soil compared to the raw solid fractions. PMID:26716355

  2. Pig slurry acidification and separation techniques affect soil N and C turnover and N2O emissions from solid, liquid and biochar fractions.

    PubMed

    Gómez-Muñoz, B; Case, S D C; Jensen, L S

    2016-03-01

    The combined effects of pig slurry acidification, subsequent separation techniques and biochar production from the solid fraction on N mineralisation and N2O and CO2 emissions in soil were investigated in an incubation experiment. Acidification of pig slurry increased N availability from the separated solid fractions in soil, but did not affect N2O and CO2 emissions. However acidification reduced soil N and C turnover from the liquid fraction. The use of more advanced separation techniques (flocculation and drainage > decanting centrifuge > screw press) increased N mineralisation from acidified solid fractions, but also increased N2O and CO2 emissions in soil amended with the liquid fraction. Finally, the biochar production from the solid fraction of pig slurry resulted in a very recalcitrant material, which reduced N and C mineralisation in soil compared to the raw solid fractions.

  3. Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

    PubMed

    Pelletier, Solenne; Vilayphiou, Nicolas; Boutroy, Stéphanie; Bacchetta, Justine; Sornay-Rendu, Elisabeth; Szulc, Pawel; Arkouche, Walid; Guebre-Egziabher, Fitsum; Fouque, Denis; Chapurlat, Roland

    2012-09-01

    We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

  4. New brittle bone disorder: report of a family with six affected individuals.

    PubMed

    Nishimura, G; Haga, N; Aoki, K; Hamazaki, M; Taniguchi, K; Iwaya, T

    1999-06-01

    We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications. PMID:10340645

  5. Leucine supplementation does not affect protein turnover and impairs the beneficial effects of endurance training on glucose homeostasis in healthy mice.

    PubMed

    Costa Júnior, José M; Rosa, Morgana R; Protzek, André O; de Paula, Flávia M; Ferreira, Sandra M; Rezende, Luiz F; Vanzela, Emerielle C; Zoppi, Cláudio C; Silveira, Leonardo R; Kettelhut, Isis C; Boschero, Antonio C; de Oliveira, Camila A M; Carneiro, Everardo M

    2015-04-01

    Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis.

  6. A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.

    PubMed

    Horwitz, Mara J; Augustine, Marilyn; Khan, Leila; Kahn, Leila; Martin, Emily; Oakley, Christine C; Carneiro, Raquel M; Tedesco, Mary Beth; Laslavic, Angela; Sereika, Susan M; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F

    2013-11-01

    Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia

  7. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group.

  8. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group. PMID:26369486

  9. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    PubMed

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage.

  10. Clinical factors affecting pathological fracture and healing of unicameral bone cysts

    PubMed Central

    2014-01-01

    Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

  11. Mof4-1 is an allele of the UPF1/IFS2 gene which affects both mRNA turnover and -1 ribosomal frameshifting efficiency.

    PubMed

    Cui, Y; Dinman, J D; Peltz, S W

    1996-10-15

    The mof4-1 (maintenance of frame) allele in the yeast Saccharomyces cerevisiae was isolated as a chromosomal mutation that increased the efficiency of -1 ribosomal frameshifting at the L-A virus frameshift site and caused loss of M1, the satellite virus of L-A. Here, we demonstrate that strains harboring the mof4-1 allele inactivated the nonsense-mediated mRNA decay pathway. The MOF4 gene was shown to be allelic to UPF1, a gene whose product is involved in the nonsense-mediated mRNA decay pathway. Although cells harboring the mof4-1 allele of the UPF1 gene lose the M1 virus, mutations in other UPF genes involved in nonsense-mediated mRNA decay maintain the M1 virus. The mof4-1 strain is more sensitive to the aminoglycoside antibiotic paromomycin than a upf1 delta strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of this drug. Further, the ifs1 and ifs2 alleles previously identified as mutations that enhance frameshifting were shown to be allelic to the UPF2 and UPF1 genes, respectively, and both ifs strains maintained M1. These results indicate that mof4-1 is a unique allele of the UPF1 gene and that the gene product of the mof4-1 allele affects both -1 ribosomal frameshifting and mRNA turnover. PMID:8896465

  12. [Paget's disease of bone: diagnosis and treatment].

    PubMed

    Winter, E M; Hamdy, N A T; de Jongh, R T; Eekhoff, E M W; Zillikens, M C; Appelman-Dijkstra, N M

    2016-01-01

    Paget's disease of bone is a focal disorder of bone remodelling that leads to changes in the shape and size of affected bones, and is associated with articular and vascular complications. The disorder is characterised by a localised increase in osteoclast number and activity in one or more affected sites while the rest of the skeleton remains unaffected. The excessive bone resorption leads to recruitment of osteoblasts to the remodelling sites, resulting in increased bone formation. This accelerated bone turnover causes deposition of bone with disorganised architecture and structural weakness. The precise aetiology is unknown. It is thought that the disease is caused by interactions between environmental and genetic factors; the nature of this interaction still has to be determined. The disease is progressive, but can be treated with a single infusion of zoledronic acid. In this manuscript three cases are described, along with a review of the current diagnostic tools and treatment. PMID:27650015

  13. Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics.

    PubMed

    Tang, Zhurong; Wang, Zhe; Qing, Fangzhu; Ni, Yilu; Fan, Yujiang; Tan, Yanfei; Zhang, Xingdong

    2015-03-01

    Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone formation which was regulated by various signal molecules. In this work, bone marrow mesenchymal stem cells (MSCs) were cultured on the surface of osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics in comparison with control (culture plate) for up to 14 days to detect the signal molecules which might be affected by the CaP ceramics. Without adding osteogenic factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix, collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various stages compared with control, thus confirmed the osteoblastic differentiation of MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP. Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance with the better osteoinductivity of BCP over HA in vivo. Altogether, these results implied that the CaP ceramics may initiate the osteoblastic differentiation of MSCs by influencing the expression of molecules in BMP/Smads pathway.

  14. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

    PubMed

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.

  15. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

    PubMed Central

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  16. Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss

    PubMed Central

    Yuan, Huaiping; Zelkha, Sami; Burkatovskaya, Marina; Gupte, Rohit; Leeman, Susan E.; Amar, Salomon

    2013-01-01

    The purpose of this study was to elucidate the role of nucleotide binding oligomerization domain-containing protein 2 (NOD2) signaling in atherosclerosis and periodontal bone loss using an Apolipoprotein E−/− (ApoE−/−) mouse model based on the proposed role of NOD2 in inflammation. NOD2−/−ApoE−/− and ApoE−/− mice fed a standard chow diet were given an oral gavage of Porphyromonas gingivalis for 15 wk. NOD2−/−ApoE−/− mice exhibited significant increases in inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and the heart compared with ApoE−/− mice. In contrast, ApoE−/− mice injected i.p. with Muramyl DiPeptide (MDP) to stimulate NOD2 and given an oral gavage of P. gingivalis displayed a reduction of serum inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and aortic sinus compared with ApoE−/− mice orally challenged but injected with saline. A reduction in body weight gain was observed in ApoE−/− mice fed a high-fat diet (HFD) and injected with MDP compared with ApoE−/− mice fed a high-fat diet but injected with saline. MDP treatment of bone marrow-derived macrophages incubated with P. gingivalis increased mRNA expressions of NOD2, Toll-like receptor 2, myeloid differentiation primary response gene 88, and receptor-interacting protein-2 but reduced the expressions of inhibitor of NF-κB kinase-β, NF-κB, c-Jun N-terminal kinase 3, and TNF-α protein levels compared with saline control, highlighting pathways involved in MDP antiinflammatory effects. MDP activation of NOD2 should be considered in the treatment of inflammatory processes affecting atherosclerosis, periodontal bone loss ,and possibly, diet-induced weight gain. PMID:24324141

  17. Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

    PubMed

    Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

    2016-06-14

    Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. PMID:27087675

  18. Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

    PubMed

    Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

    2016-06-14

    Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity.

  19. Inulin, oligofructose and bone health: experimental approaches and mechanisms.

    PubMed

    Weaver, Connie M

    2005-04-01

    Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored. A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions.

  20. Bone biopsy in the diagnosis of renal osteodystrophy.

    PubMed

    Spasovski, Goce B

    2004-01-01

    When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse manifestations in bone cells and structure as well as the rate of bone turnover. In ESRF when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology named renal osteodystrophy (ROD). On the other hand, survival rates of patients on dialysis have increased with improved dialytic therapy and the resultant increased duration of dialysis has led to a rise in renal osteodystrophy. Because this metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH levels are commonly used to assess bone turnover in dialyzed patients. However, it is found that serum PTH levels between 65 and 450 pg/ml seen in the majority of dialysis patients are not predictive of the underlying bone disease. To date, bone biopsy is the most powerful and informative diagnostic tool to provide important information on precisely the type of renal osteodystrophy affecting patients, the degree of severity of the lesions, and the presence and amount of aluminum and strontium deposition in bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered as an invasive procedure, bone biopsy has been proven as safe and free from major complications besides pain, haematoma or wound infections, but the operator's experience and skill is important in minimizing morbidity. Alternatives to bone biopsy continue to be pursued, but the non-invasive bone markers have not been proven to hold sufficient diagnostic performance related to the bone turnover, mineralization process and bone cell abnormality. At present however, the transiliac bone biopsy remains the golden standard in the diagnosis of renal osteodystrophy. PMID:15735537

  1. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  2. [Bone quality and strength relating with bone remodeling].

    PubMed

    Mori, Satoshi

    2016-01-01

    The bone has the functions of mineral reservoir and mechanical support as skeleton. Bone remodeling is the adult mode of bone metabolism, replacing old bone tissue to new one. Bone strength is determined by bone volume, structure and quality such as micro damage, degree of mineralization and collagen cross linkage, which are all controlled by bone remodeling. Bone strength decreases under high turn-over condition by decreasing bone volume and deterioration of bone structure, which also decreases under low turn-over condition by increased micro damage, increasing mineralization and AGE collagen cross linkage.

  3. Bone resorption is affected by follicular phase length in female rotating shift workers.

    PubMed Central

    Lohstroh, Pete N; Chen, Jiangang; Ba, Jianming; Ryan, Louise M; Xu, Xiping; Overstreet, James W; Lasley, Bill L

    2003-01-01

    Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT. PMID:12676625

  4. Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion.

    PubMed

    Simann, Meike; Schneider, Verena; Le Blanc, Solange; Dotterweich, Julia; Zehe, Viola; Krug, Melanie; Jakob, Franz; Schilling, Tatjana; Schütze, Norbert

    2015-09-01

    Heparins are broadly used for the prevention and treatment of thrombosis and embolism. Yet, osteoporosis is considered to be a severe side effect in up to one third of all patients on long-term treatment. However, the mechanisms underlying this clinical problem are only partially understood. To investigate if heparin affects differentiation of skeletal precursors, we examined the effects of heparin on the osteogenic and adipogenic lineage commitment and differentiation of primary human bone marrow stromal cells (hBMSCs). Due to the known inverse relationship between adipogenesis and osteogenesis and the capacity of pre-differentiated cells to convert into the respective other lineage, we also determined heparin effects on osteogenic conversion and adipogenic differentiation/conversion. Interestingly, heparin did not only significantly increase mRNA expression and enzyme activity of the osteogenic marker alkaline phosphatase (ALP), but it also promoted mineralization during osteogenic differentiation and conversion. Furthermore, the mRNA expression of the osteogenic marker bone morphogenic protein 4 (BMP4) was enhanced. In addition, heparin administration partly prevented adipogenic differentiation and conversion demonstrated by reduced lipid droplet formation along with a decreased expression of adipogenic markers. Moreover, luciferase reporter assays, inhibitor experiments and gene expression analyses revealed that heparin had putative permissive effects on osteogenic signaling via the BMP pathway and reduced the mRNA expression of the Wnt pathway inhibitors dickkopf 1 (DKK1) and sclerostin (SOST). Taken together, our data show a rather supportive than inhibitory effect of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further studies will have to investigate the net effects of heparin administration on bone formation versus bone resorption in vivo to unravel the molecular mechanisms of heparin-associated osteoporosis and reconcile

  5. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is

  6. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  7. Contextual Factors Related to Elementary Principal Turnover

    ERIC Educational Resources Information Center

    Partlow, Michelle C.

    2007-01-01

    The issue of school leadership instability and how it affects schools and student achievement has been studied. The question of how to predict turnover of the principal remains an unknown. The purpose of this research was to search for possible relationships between certain contextual variables and principal turnover and to test the independent…

  8. Employee Turnover: Evidence from a Case Study.

    ERIC Educational Resources Information Center

    Borland, Jeff

    1997-01-01

    Patterns of employee turnover from a medium-sized law firm in Australia were examined in regard to theories of worker mobility (matching, sectoral shift, and incentive). Results support a role for matching effects, but personnel practices affect the timing of turnover. Matching and incentive-based theories do not explain the high rates of turnover…

  9. Thyroid status affects number and localization of thyroid hormone receptor expressing mast cells in bone marrow.

    PubMed

    Siebler, T; Robson, H; Bromley, M; Stevens, D A; Shalet, S M; Williams, G R

    2002-01-01

    Thyroid hormone (T(3)) plays a key role in endochondral ossification. The process relies on the coordinated synthesis and degradation of cartilage matrix and is disrupted in juvenile hypothyroidism, leading to abnormal skeletal development. Mast cells synthesize and store matrix-degrading enzymes. We examined whether thyroid status influences skeletal mast cell distribution in growing rats to determine whether they might modulate the actions of T(3) in bone. Tibiae were collected for histological, histochemical, immunohistochemical, and immunofluorescence analysis. Mast cells were increased throughout the bone marrow in hypothyroid rats compared with euthyroid, thyrotoxic, and hypothyroid-thyroxine replaced animals. Large numbers were present in metaphyseal marrow adjacent to the growth plate in hypothyroid animals and cells were distributed evenly throughout the marrow. Very few mast cells were present in metaphyseal marrow in other groups, but their numbers increased with increasing distance from the growth plate. T(3) receptor alpha1 (TRalpha1) was expressed in the nucleus and cytoplasm of skeletal mast cells, whereas TRalpha2 and TRbeta1 were restricted to the cytoplasm. Localization of TRs was not affected by altered thyroid status. Thus, disrupted endochondral ossification in hypothyroidism may be mediated in part by skeletal mast cells, which express TR proteins and may function as T(3) target cells.

  10. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    PubMed

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-01-01

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active. PMID:26474791

  11. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    PubMed

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-12-16

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active.

  12. Diet calcium level but not calcium supplement particle size affects bone density and mechanical properties in ovariectomized rats.

    PubMed

    Shahnazari, Mohammad; Martin, Berdine R; Legette, Leecole L; Lachcik, Pamela J; Welch, Jo; Weaver, Connie M

    2009-07-01

    Calcium (Ca) supplements, especially Ca carbonate (CaCO3), are the main alternative sources of dietary Ca and an important part of a treatment regimen for osteoporosis, the most common metabolic bone disorder of aging and menopause. In a female ovariectomized (OVX) rat model for studying postmenopausal osteoporosis, we tested the hypothesis that a small compared with a large particle size of CaCO3 (13.0- vs. 18.5-mum geometric diameter) would result in increased Ca balance and subsequently bone mass and that this would be affected by dietary Ca level. We used 6-mo-old rats that were OVX either at 6 or 3 mo of age as models of early or stable menopausal status, respectively. The rats received semipurified diets that contained either 0.4 or 0.2% dietary Ca provided from CaCO3 of 2 particle sizes. A group of Sham-operated rats with intact ovaries served as control and were fed 0.4% dietary Ca from large particles. Estrogen deficiency as a result of ovariectomy had an adverse effect on bone density, mineral content, and bone mechanical properties (P < 0.001). Reducing dietary Ca from 0.4 to 0.2% resulted in significant adverse effects on bone density and mechanical properties (P < 0.001). The particle size of CaCO3 did not affect total Ca balance, bone dual energy X-ray absorptiometry and peripheral quantitative computed tomography indices, bone ash and Ca content, or the mechanical determinants of bone strength. We conclude that a decrease in particle size of CaCO3 to 70% of that typically found in Ca supplements does not provide a benefit to overall Ca metabolism or bone characteristics and that the amount of Ca consumed is of greater influence in enhancing Ca nutrition and skeletal strength.

  13. High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

    PubMed

    Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

    2015-01-01

    Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

  14. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior.

    PubMed

    Sterling, Julie A; Edwards, James R; Martin, T John; Mundy, Gregory R

    2011-01-01

    It is increasingly evident that the microenvironment of bone can influence the cancer phenotype in many ways that favor growth in bone. The ability of cancer cells to adhere to bone matrix and to promote osteoclast formation are key requirements for the establishment and growth of bone metastases. Several cytokine products of breast cancers (e.g. PTHrP, IL-11, IL-8) have been shown to act upon host cells of the bone microenvironment to promote osteoclast formation, allowing for excessive bone resorption. The increased release of matrix-derived growth factors, especially TGF-β, acts back upon the tumor to facilitate further tumor expansion and enhance cytokine production, and also upon osteoblasts to suppress bone formation. This provides a self-perpetuating cycle of bone loss and tumor growth within the skeleton. Other contributing factors favoring tumor metastasis and colonization in bone include the unique structure and stiffness of skeletal tissue, along with the diverse cellular composition of the marrow environment (e.g. bone cells, stromal fibroblasts, immune cells), any of which can contribute to the phenotypic changes that can take place in metastatic deposits that favor their survival. Additionally, it is also apparent that breast cancer cells begin to express different bone specific proteins as well as proteins important for normal breast development and lactation that allow them to grow in bone and stimulate bone destruction. Taken together, these continually emerging areas of study suggest new potential pathways important in the pathogenesis of bone metastasis and potential areas for targeting therapeutics.

  15. Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized control trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although consuming dietary protein above current recommendations during energy deficit enhances blood lipid profiles and preserves lean body mass, concerns have been raised regarding effects of high-protein diets on bone health. To determine whether calcium homeostasis and bone turnover are affected...

  16. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

    PubMed

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-03-25

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint.

  17. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    PubMed Central

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  18. Dietary supplements and physical exercise affecting bone and body composition in frail elderly persons.

    PubMed Central

    de Jong, N; Chin A Paw, M J; de Groot, L C; Hiddink, G J; van Staveren, W A

    2000-01-01

    OBJECTIVES: This study determined the effect of enriched foods and all-around physical exercise on bone and body composition in frail elderly persons. METHODS: A 17-week randomized, controlled intervention trial, following a 2 x 2 factorial design--(1) enriched foods, (2) exercise, (3) both, or (4) neither--was performed in 143 frail elderly persons (aged 78.6 +/- 5.6 years). Foods were enriched with multiple micronutrients; exercises focused on skill training, including strength, endurance, coordination, and flexibility. Main outcome parameters were bone and body composition. RESULTS: Exercise preserved lean mass (mean difference between exercisers and non-exercisers: 0.5 kg +/- 1.2 kg; P < .02). Groups receiving enriched food had slightly increased bone mineral density (+0.4%), bone mass (+0.6%), and bone calcium (+0.6%) compared with groups receiving non-enriched foods, in whom small decreases of 0.1%, 0.2%, and 0.4%, respectively, were found. These groups differed in bone mineral density (0.006 +/- 0.020 g/cm2; P = .08), total bone mass (19 +/- g; P = .04), and bone calcium (8 +/- 21 g; P = .03). CONCLUSIONS: Foods containing a physiologic dose of micronutrients slightly increased bone density, mass, and calcium, whereas moderately intense exercise preserved lean body mass in frail elderly persons. PMID:10846514

  19. Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

    PubMed

    Lambert, Jennifer; Lamothe, Jeremy M; Zernicke, Ronald F; Auer, Roland N; Reimer, Raylene A

    2005-02-01

    The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass. PMID:15585686

  20. Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis

    PubMed Central

    Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

    2015-01-01

    Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. PMID:25945040

  1. Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis.

    PubMed

    Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

    2015-01-01

    Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression. PMID:25945040

  2. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    PubMed

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone

  3. Evaluating bone quality in patients with chronic kidney disease

    PubMed Central

    Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

    2013-01-01

    Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

  4. Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.

    PubMed

    Holen, I; Walker, M; Nutter, F; Fowles, A; Evans, C A; Eaton, C L; Ottewell, P D

    2016-03-01

    Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER+ve (MCF7, T47D) or ER-ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 μg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER+ve cells to bone in 80-100 % of animals whereas bone metastases from ER-ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER+ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER-ve cells require increased osteoclast activity to grow in bone whereas ER+ve cells do not. Zol does not affect ER+ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER+ve breast cancer cells in bone.

  5. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

    PubMed

    Fassio, A; Idolazzi, L; Jaber, M A; Dartizio, C; Viapiana, O; Rossini, M; Gatti, D

    2016-01-01

    Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself. PMID:27608794

  6. Audiologic Patterns of Otic Capsule Preserving Temporal Bone Fracture: Effects of the Affected Subsites

    PubMed Central

    Kim, So Young; Kim, Yoon Joong; Kim, Young Ho; Park, Min-Hyun

    2016-01-01

    Objectives. This study was aimed to assess the relationship between the type of temporal bone area involved and conductive hearing loss. Methods. We enrolled 97 patients who visited the otolaryngology clinics of Seoul National University Hospital or Boramae Medical Center, Seoul Metropolitan Government-Seoul National University with temporal bone fracture between January 2004 and January 2014. Audiometric parameters, including initial and improved air-bone (AB) conduction gap values, were reviewed in accordance with the temporal bone computed tomography (external auditory canal [EAC], middle ear [ME], mastoid [M], and ossicle [O]). Results. Patients with ossicular chain involvement exhibited a larger AB gap compared to those with no ossicular chain involvement at 250, 1,000, 2,000, and 4,000 Hz. Among the groups without ossicular chain involvement, the initial AB gap was largest in patients with EAC+ME+M involvement, followed by the ME+M and M-only involvement groups. The greatest improvement in the AB gap was observed in the EAC+ME+M group followed by the ME+M and M-only groups, irrespective of ossicular chain involvement. Improvements in AB gap values were smallest at 2,000 Hz. Conclusion. Conductive hearing loss pattern differed according to the temporal bone area involved. Therefore, areas such as the hematoma and hemotympanum, as well as the fracture line of the temporal bone area, must be evaluated to predict audiologic patterns with otic capsule preserving temporal bone fracture. PMID:27337953

  7. Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells

    PubMed Central

    2013-01-01

    Background Mesenchymal stromal cells (MSCs) are attractive for cell-based therapies ranging from regenerative medicine and tissue engineering to immunomodulation. However, clinical efficacy is variable and it is unclear how the phenotypes defining bone marrow (BM)-derived MSCs as well as donor characteristics affect their functional properties. Methods BM-MSCs were isolated from 53 (25 female, 28 male; age: 13 to 80 years) donors and analyzed by: (1) phenotype using flow cytometry and cell size measurement; (2) in vitro growth kinetics using population doubling time; (3) colony formation capacity and telomerase activity; and (4) function by in vitro differentiation capacity, suppression of T cell proliferation, cytokines and trophic factors secretion, and hormone and growth factor receptor expression. Additionally, expression of Oct4, Nanog, Prdm14 and SOX2 mRNA was compared to pluripotent stem cells. Results BM-MSCs from younger donors showed increased expression of MCAM, VCAM-1, ALCAM, PDGFRβ, PDL-1, Thy1 and CD71, and led to lower IL-6 production when co-cultured with activated T cells. Female BM-MSCs showed increased expression of IFN-γR1 and IL-6β, and were more potent in T cell proliferation suppression. High-clonogenic BM-MSCs were smaller, divided more rapidly and were more frequent in BM-MSC preparations from younger female donors. CD10, β1integrin, HCAM, CD71, VCAM-1, IFN-γR1, MCAM, ALCAM, LNGFR and HLA ABC were correlated to BM-MSC preparations with high clonogenic potential and expression of IFN-γR1, MCAM and HLA ABC was associated with rapid growth of BM-MSCs. The mesodermal differentiation capacity of BM-MSCs was unaffected by donor age or gender but was affected by phenotype (CD10, IFN-γR1, GD2). BM-MSCs from female and male donors expressed androgen receptor and FGFR3, and secreted VEGF-A, HGF, LIF, Angiopoietin-1, basic fibroblast growth factor (bFGF) and NGFB. HGF secretion correlated negatively to the expression of CD71, CD140b and

  8. Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

    PubMed Central

    Leung, J.; Zhang, Y. F.; Bauer, D.; Ensrud, K. E.; Barrett-Connor, E.; Leung, P. C.

    2013-01-01

    Summary In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. Introduction Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. Methods Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. Results Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm2) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. Conclusion Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID:22080379

  9. Prevention of vascular calcification with bisphosphonates without affecting bone mineralization: a new challenge?

    PubMed

    Neven, Ellen G; De Broe, Marc E; D'Haese, Patrick C

    2009-03-01

    Arterial calcification has been found to coexist with bone loss. Bisphosphonates, used as standard therapy for osteoporosis, inhibit experimentally induced vascular calcification, offering perspectives for the treatment of vascular calcification in renal failure patients. However, Lomashvili et al. report that the doses of etidronate and pamidronate that are effective in attenuating aortic calcification also decrease bone formation and mineralization in uremic rats, limiting their therapeutic use as anticalcifying agents.

  10. Bone quality is affected by food restriction and by nutrition-induced catch-up growth.

    PubMed

    Pando, Rakefet; Masarwi, Majdi; Shtaif, Biana; Idelevich, Anna; Monsonego-Ornan, Efrat; Shahar, Ron; Phillip, Moshe; Gat-Yablonski, Galia

    2014-12-01

    Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. PMID:25248555

  11. Frequency of Teriparatide Administration Affects the Histological Pattern of Bone Formation in Young Adult Male Mice.

    PubMed

    Yamamoto, Tomomaya; Hasegawa, Tomoka; Sasaki, Muneteru; Hongo, Hiromi; Tsuboi, Kanako; Shimizu, Tomohiro; Ota, Masahiro; Haraguchi, Mai; Takahata, Masahiko; Oda, Kimimitsu; Luiz de Freitas, Paulo Henrique; Takakura, Aya; Takao-Kawabata, Ryoko; Isogai, Yukihiro; Amizuka, Norio

    2016-07-01

    Evidence supports that daily and once-weekly administration of teriparatide, human (h)PTH(1-34), enhance bone mass in osteoporotic patients. However, it is uncertain whether different frequencies of hPTH(1-34) administration would induce bone formation similarly in terms of quantity and quality. To investigate that issue, mice were subjected to different frequencies of PTH administration, and their bones were histologically examined. Frequencies of administration were 1 time/2 days, 1 time a day, and 2 and 4 times a day. Mice were allocated to either to control or to 3 different dosing regimens: 80 μg/kg of hPTH(1-34) per injection (80 μg/kg per dose), 80 μg/kg of hPTH(1-34) per day (80 μg/kg · d), or 20 μg/kg of hPTH(1-34) per day (20 μg/kg · d). With the regimens of 80 μg/kg per dose and 80 μg/kg · d, high-frequency hPTH(1-34) administration increased metaphyseal trabecular number. However, 4 doses per day induced the formation of thin trabeculae, whereas the daily PTH regimen resulted in thicker trabeculae. A similar pattern was observed with the lower daily hPTH(1-34) dose (20 μg/kg · d): more frequent PTH administration led to the formation of thin trabeculae, showing a thick preosteoblastic cell layer, several osteoclasts, and scalloped cement lines that indicated accelerated bone remodeling. On the other hand, low-frequency PTH administration induced new bone with mature osteoblasts lying on mildly convex surfaces representative of arrest lines, which suggests minimodeling-based bone formation. Thus, high-frequency PTH administration seems to increase bone mass rapidly by forming thin trabeculae through accelerated bone remodeling. Alternatively, low-frequency PTH administration leads to the formation of thicker trabeculae through bone remodeling and minimodeling. PMID:27227535

  12. Increasing fluid milk favorably affects bone mineral density responses to resistance training in adolescent boys.

    PubMed

    Volek, Jeff S; Gómez, Ana L; Scheett, Timothy P; Sharman, Matthew J; French, Duncan N; Rubin, Martyn R; Ratamess, Nicholas A; McGuigan, Michael M; Kraemer, William J

    2003-10-01

    This study examined the effects of increasing milk on bone and body composition responses to resistance training in adolescents. Twenty-eight boys (13 to 17 years of age) were randomly assigned to consume, in addition to their habitual diet, 3 servings/day of 1% fluid milk (n=14) or juice not fortified with calcium (n=14) while engaged in a 12-week resistance-training program. For all subjects combined, there were significant (Pbone mineral content (+3.6%), bone mineral density (+1.8%), and maximal strength in the squat (+43%) and bench press (+23%). Compared with juice, the milk group had a significantly greater increase in bone mineral density (0.014 vs 0.028 g/cm(2)). Increasing intake of milk in physically active adolescent boys may enhance bone health.

  13. Optimizing Bone Health in Duchenne Muscular Dystrophy

    PubMed Central

    Buckner, Jason L.; Bowden, Sasigarn A.; Mahan, John D.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. PMID:26124831

  14. Hoof position during limb loading affects dorsoproximal bone strains on the equine proximal phalanx.

    PubMed

    Singer, Ellen; Garcia, Tanya; Stover, Susan

    2015-07-16

    Sagittal fractures of the proximal phalanx (P1) in the racehorse appear to be associated with turf racing surfaces, which are known to restrict forward slide of the foot at impact. We hypothesized that restriction of forward foot slip would result in higher P1 bone strains during metacarpophalangeal joint (MCPJ) hyperextension. Unilateral limbs from six equine cadavers were instrumented with strain gauges and bone reference markers to measure dorsoproximal P1 bone strains and MCPJ extension, collateromotion and axial rotation during in vitro limb loading to 10,500 N. By limiting movement of the distal actuator platform, three different foot conditions (forward, free, and restricted) were applied in a randomised block design. Bone reference markers, recorded by video, were analyzed to determine motion of P1 relative to MC3. Rosette strain data were reduced to principal and shear magnitudes and directions. A mixed model ANOVA determined the effect of foot position on P1 bone strains and MCPJ angles. At 10,000 N load, the restricted condition resulted in higher P1 axial compressive (p=0.015), maximum shear (p=0.043) and engineering shear (p=0.046) strains compared to the forward condition. The restricted condition had higher compressive (p=0.025) and lower tensile (p=0.043) principal strains compared to the free condition. For the same magnitude of principal or shear strains, axial rotation and collateromotion angles were greatest for the restricted condition. Therefore, the increase in P1 principal compressive and shear bone strains associated with restricted foot slip indicate that alterations in foot:ground interaction may play a role in fracture occurrence in horses.

  15. Gorham-Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage.

    PubMed

    Morimoto, Noriko; Ogiwara, Hideki; Miyazaki, Osamu; Kitamuara, Masayuki; Nishina, Sachiko; Nakazawa, Atsuko; Maekawa, Takanobu; Morota, Nobuhito

    2013-09-01

    Gorham-Stout syndrome is a rare disorder characterized by progressive osteolysis that leads to the disappearance of bone. Lymphvascular proliferation causes the local destruction of bony tissue. Owing to the low incidence of this syndrome, little is known about its etiology or treatment. We present an 11-year-old girl with Gorham-Stout syndrome that involved right petrous apex in temporal bone and upper clivus, which cause intracranial pressure increase and cerebrospinal fluid (CSF) leakage. The patient required surgical repair of CSF leakage by extradural middle fossa approach with temporal fascia flap. Combined treatment with interferon and propranolol prevented the progression of osteolysis.

  16. The behavior of the micro-mechanical cement-bone interface affects the cement failure in total hip replacement

    PubMed Central

    Waanders, Daan; Janssen, Dennis; Mann, Kenneth A.; Verdonschot, Nico

    2010-01-01

    In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle was investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro FEA-models. Case II, III and IV were analyzed using data from a stiff and a compliant micro-FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement-bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seem to be necessary. PMID:21036358

  17. Rye affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in Turkey poults.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Hargis, Billy M; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  18. Bone disease in primary hypercalciuria

    PubMed Central

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH

  19. Inhibition of bone resorption and growth of breast cancer in the bone microenvironment.

    PubMed

    Buijs, Jeroen T; Que, Ivo; Löwik, Clemens W G M; Papapoulos, Socrates E; van der Pluijm, Gabri

    2009-02-01

    Breast cancer frequently metastasizes to bone, where tumor cells induce osteoclasts to locally destroy bone. During bone resorption, growth factors are locally released that may support bone metastatic growth. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates and osteoprotegerin (OPG), are available for bone. We examined the hypothesis that inhibition of bone resorption by two different mechanisms may also affect the growth of cancer cells in bone. For this, we tested the effects of high doses of OPG and zoledronic acid (ZOL) on progression of MDA-231-B/Luc+ breast cancer cells in the bone microenvironment using whole body bioluminescent reporter imaging (BLI). Both treatments significantly inhibited the development of radiographically detectable osteolytic lesions. Histologic examination corroborated the radiographic findings, showing that both treatments preserved the integrity of bone trabeculae and prevented bone destruction (significantly higher trabecular bone volumes vs. vehicle). However, whereas practically no TRAcP-positive osteoclasts were observed in tibiae preparations of animals treated with Fc-OPG, TRAcP-positive osteoclasts were still present in the animals treated with ZOL. Intra-bone tumor burden was reduced with ZOL and Fc-OPG treatment. Although there appeared to be a trend for less overall total tumor burden upon treatment with both compounds, this was not significant as assessed by BLI and histomorphometric analysis due to the extramedullary growth of cancer cells which was not affected by these treatments. Collectively, anti-resorptive agents with different mechanisms of action - ZOL and OPG - significantly reduced cancer-induced osteolysis and intra-osseous tumor burden, but failed to restrain local tumor growth. However, interference with the bone micro-environmental growth support could still be of therapeutic relevance when given to patients early in the course of bone metastatic disease.

  20. Vitamin B-12 supplementation of rural Mexican women changes biochemical B-12 status indicators but does not affect hematology or a bone turnover marker

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on the high prevalence of low serum vitamin B-12 concentrations and low dietary intake of the vitamin in Latin American studies including research in Mexico, it appears that vitamin B-12 deficiency is common. Whether this is associated with adverse effects on human function is unknown. To eval...

  1. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis.

    PubMed

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M; Giannoudis, Peter V

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  2. Disruption of glucocorticoid signaling in chondrocytes delays metaphyseal fracture healing but does not affect normal cartilage and bone development

    PubMed Central

    Tu, Jinwen; Henneicke, Holger; Zhang, Yaqing; Stoner, Shihani; Cheng, Tegan L.; Schindeler, Aaron; Chen, Di; Tuckermann, Jan; Cooper, Mark S.; Seibel, Markus J.; Zhou, Hong

    2014-01-01

    States of glucocorticoid excess are associated with defects in chondrocyte function. Most prominently there is a reduction in linear growth but delayed healing of fractures that require endochondral ossification to also occur. In contrast, little is known about the role of endogenous glucocorticoids in chondrocyte function. As glucocorticoids exert their cellular actions through the glucocorticoid receptor (GR), we aimed to elucidate the role of endogenous glucocorticoids in chondrocyte function in vivo through characterization of tamoxifen-inducible chondrocyte-specific GR knockout (chGRKO) mice in which the GR was deleted at various post-natal ages. Knee joint architecture, cartilage structure, growth plates, intervertebral discs, long bone length and bone micro-architecture were similar in chGRKO and control mice at all ages. Analysis of fracture healing in chGRKO and control mice demonstrated that in metaphyseal fractures, chGRKO mice formed a larger cartilaginous callus at 1 and 2 week post-surgery, as well as a smaller amount of well-mineralized bony callus at the fracture site 4 week post-surgery, when compared to control mice. In contrast, chondrocyte-specific GR knockout did not affect diaphyseal fracture healing. We conclude that endogenous GC signaling in chondrocytes plays an important role during metaphyseal fracture healing but is not essential for normal long bone growth. PMID:25193158

  3. Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross.

    PubMed

    Norgard, Elizabeth A; Lawson, Heather A; Pletscher, L Susan; Wang, Bing; Brooks, Victoria R; Wolf, Jason B; Cheverud, James M

    2011-04-01

    Previous studies on the LG,SM advanced intercross line have identified approximately 40 quantitative trait loci (QTL) for long -bone (humerus, ulna, femur, and tibia) lengths. In this study, long-bone-length QTL were fine-mapped in the F(34) generation (n = 1424) of the LG,SM advanced intercross. Environmental effects were assessed by dividing the population by sex between high-fat and low-fat diets, producing eight sex/diet cohorts. We identified 145 individual bone-length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from previous studies, 35 were new traits significant at previously identified loci, and 41 were novel QTL. Many QTL affected only a subset of the population based on sex and/or diet. Eight of ten known skeletal growth genes were upregulated in 3-week-old LG/J male proximal tibial growth plates relative to SM/J. The sequences of parental strains LG/J and SM/J indicated the presence of over half a million polymorphisms in the confidence intervals of these 45 QTL. We examined 526 polymorphisms and found that 97 represented radical changes to amino acid composition while 40 were predicted to be deleterious to protein function. Additional experimentation is required to understand how changes in gene regulation or protein function can alter the genetic architecture and interact with the environment to produce phenotypic variation.

  4. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells.

  5. Antecedents of Norwegian Beginning Teachers' Turnover Intentions

    ERIC Educational Resources Information Center

    Tiplic, Dijana; Brandmo, Christian; Elstad, Eyvind

    2015-01-01

    This study aims at exploring several individual, organizational, and contextual factors that may affect beginning teachers' turnover intentions during their first years of practice. The sample consists of 227 beginning teachers (69% female and 31% male) from 133 schools in Norway. The results show four important antecedents of beginning teachers'…

  6. Predicting Turnover Intentions and Turnover Behavior: A Multivariate Analysis.

    ERIC Educational Resources Information Center

    Parasuraman, Saroj

    1982-01-01

    Assessed the relative influence of personal, attitudinal, and behavioral variables on behavioral intentions and voluntary turnover among nonsupervisory plant workers. Results show that personal variables have little direct effect on turnover; rather, their influence on turnover is channeled through their effects on behavioral intentions. (Author)

  7. QTL mapping of genetic determinants of lipoprotein metabolism in mice: Mutations of the apolipoprotein A-II gene affecting lipoprotein turnover

    SciTech Connect

    Weinreb, A.; Purcell-Huynh, D.A.; Castellani, L.W.

    1994-09-01

    Cholesterol and lipoproteins represent important risk factors for atherosclerosis. In order to better understand the genes involved in determining lipoprotein levels, quantitative trait locus (QTL) mapping was performed using a cross between NZB and SM/J mice. Significant LOD scores for loci determining total cholesterol, HDL cholesterol, LDL and VLDL cholesterol, triglycerides, free fatty acids, and apolipoprotein A-II (apoA-II) were obtained. NZB mice have a 7-10 fold higher apoA-II level SM/J. LOD scores of 19.6 (chow) and 10.3 (high fat) were obtained at the apoA-II gene locus. Comparison of apoA-II levels by apoA-II genotype reveals that {approximately}30% of the variance in apoA-II levels can be accounted for by differences within the apoA-II gene. Northern analysis of mRNA from NZB and SM/J mice fed a high fat diet failed to show any significant differences in mRNA levels. The rates of apoA-II protein synthesis relative to total protein synthesis between the two strains were similar, with a rate of 0.16% for NZB and 0.18% for SM/J. Sequencing of NZB and SM/J apoA-II cDNAs revealed a pro5 to gln5 substitution in SM/J. Therefore, differences in the apoA-II levels between NZB and SM/J may be partly due to a structural difference in apoA-II resulting in an increased rate of apoA-II clearance in SM/J. A coincident QTL for HDL at the same chromosome 1 locus suggests that a structural difference in apoA-II may be affecting the rate of HDL clearance. It is of interest to note that the pro5 to gln5 substitution leads to apoA-II amyloid deposition in the SAM mouse.

  8. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk.

    PubMed

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  9. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk

    PubMed Central

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  10. Vascular calcification and renal bone disorders.

    PubMed

    Lu, Kuo-Cheng; Wu, Chia-Chao; Yen, Jen-Fen; Liu, Wen-Chih

    2014-01-01

    At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC. PMID:25136676

  11. Increased bone morphogenetic protein 7 signalling in the kidneys of dogs affected with a congenital portosystemic shunt.

    PubMed

    van Dongen, Astrid M; Heuving, Susanne M; Tryfonidou, Marianna A; van Steenbeek, Frank G; Rothuizen, Jan; Penning, Louis C

    2015-05-01

    Dogs with a congenital portosystemic shunt (CPSS) often have enlarged and hyper-filtrating kidneys. Although expression of different growth factors has been well-described in the livers of dogs affected with a CPSS, their expression in the kidneys has yet to be determined. Bone morphogenetic protein 7 (BMP-7), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β have been implicated in renal development (BMP-7, HGF) or the onset of renal fibrosis (TGF-β). Moreover, BMP-7 and HGF have protective properties in renal fibrosis. In this study, the expression and activity of BMP-7 were investigated in renal biopsies obtained from 13 dogs affected with a CPSS and compared to similar samples from age-matched healthy control dogs. Both quantitative reverse-transcriptase PCR and Western blotting showed up-regulated BMP-7 signalling in kidneys of CPPS-affected dogs. These research findings may help to explain the renal pathology/dysfunction in dogs affected with a CPSS.

  12. Carpal Tunnel Cross-Sectional Area Affected by Soft Tissues Abutting the Carpal Bones.

    PubMed

    Gabra, Joseph N; Li, Zong-Ming

    2013-02-01

    The carpal tunnel accommodates free movement of its contents, and the tunnel's cross-sectional area is a useful morphological parameter for the evaluation of the space available for the carpal tunnel contents and of potential nerve compression in the tunnel. The osseous boundary of the carpal bones as the dorsal border of the carpal tunnel is commonly used to determine the tunnel area, but this boundary contains soft tissues such as numerous intercarpal ligaments and the flexor carpi radialis tendon. The aims of this study were to quantify the thickness of the soft tissues abutting the carpal bones and to investigate how this soft tissue influences the calculation of the carpal tunnel area. Magnetic resonance images were analyzed for eight cadaveric specimens. A medical balloon with a physiological pressure was inserted into an evacuated tunnel to identify the carpal tunnel boundary. The balloon-based (i.e. true carpal tunnel) and osseous-based carpal tunnel boundaries were extracted and divided into regions corresponding to the hamate, capitate, trapezoid, trapezium, and transverse carpal ligament (TCL). From the two boundaries, the overall and regional soft tissue thicknesses and areas were calculated. The soft tissue thickness was significantly greater for the trapezoid (3.1±1.2mm) and trapezium (3.4±1.0mm) regions than for the hamate (0.7±0.3mm) and capitate (1.2±0.5mm) regions. The carpal tunnel area using the osseous boundary (243.0±40.4mm(2)) was significantly larger than the balloon-based area (183.9±29.7mm(2)) with a ratio of 1.32. In other words, the carpal tunnel area can be estimated as 76% (= 1/1.32) of the osseous-based area. The abundance of soft tissue in the trapezoid and trapezium regions can be attributed mainly to the capitate-trapezium ligament and the flexor carpi radialis tendon. Inclusion of such soft tissue leads to overestimations of the carpal tunnel area. Correct quantification of the carpal tunnel area aids in examining carpal

  13. Organizational culture, job satisfaction, and clinician turnover in primary care.

    PubMed

    Hall, Charles B; Brazil, Kevin; Wakefield, Dorothy; Lerer, Trudy; Tennen, Howard

    2010-04-01

    The purpose of this study is to examine how organizational culture and job satisfaction affect clinician turnover in primary care pediatric practices. One hundred thirty clinicians from 36 primary care pediatric practices completed the Primary Care Organizational Questionnaire (PCOQ), which evaluates interactions among members of the practice and job-related attributes measuring 8 organizational factors, along with a separate 3-item instrument measuring job satisfaction. Random effects logistic models were used to assess the associations between job satisfaction, the organizational factors from the PCOQ, and clinician turnover over the subsequent year. All 8 measured organizational factors from the PCOQ, particularly perceived effectiveness, were associated with job satisfaction. Five of the 8 organizational factors were also associated with clinician turnover. The effects of the organizational factors on turnover were substantially reduced in a model that included job satisfaction; only 1 organizational factor, communication between clinicians and nonclinicians, remained significant (P = .05). This suggests that organizational culture affects subsequent clinician turnover primarily through its effect on job satisfaction. Organizational culture, in particular perceived effectiveness and communication, affects job satisfaction, which in turn affects clinician turnover in primary care pediatric practices. Strategies to improve job satisfaction through changes in organizational culture could potentially reduce clinician turnover. PMID:23804066

  14. Does light scattering affect the OCT quantitation of redox state of cytochrome oxidase in bone tissue?

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Wang, Ruikang K.; El Haj, Alicia

    2002-06-01

    In our previous report, we have presented the possibility of optical coherence tomography (OCT) to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone tissue. The previous results showed that reduction of the enzyme in periosteal tissue leads to a change in attenuation coefficient of 1.68 +/- 0.67mm-1 by OCT measurements. The new results from cultured cells fixed in 300 (mu) l agarose plug showed the difference in attenuation coefficient is 0.26+-0.10 mm-1 (n = 9) for 7x106 astrocytoma cells and 0.28+-0.13 mm-1 (n = 7) for 20x106 astrocytoma cells in agarose plug, respectively between cells with oxidised and reduced enzyme at 820nm. A decrease in attenuation coefficient of 0.35+-0.09 mm-1 (n = 4) for 10 million SKMES cells in agarose was also observed with the redox shift of CytOx. The absorption coefficient of the oxidized-reduced form of CytOx is measured approximately 8.4+-1.5x10-3/mm (n=3) and 8.2+-1.0x10-3/mm (n=3) at 820nm for astrocytoma cells and rat periosteum respectively by means of a biochemical assay. Thereby it can be seen that the change in attenuation coefficient of cultured cells with redox shift of CytOx mainly results from the scattering change.

  15. The rice FISH BONE gene encodes a tryptophan aminotransferase, which affects pleiotropic auxin-related processes.

    PubMed

    Yoshikawa, Takanori; Ito, Momoyo; Sumikura, Tsuyoshi; Nakayama, Akira; Nishimura, Takeshi; Kitano, Hidemi; Yamaguchi, Isomaro; Koshiba, Tomokazu; Hibara, Ken-Ichiro; Nagato, Yasuo; Itoh, Jun-Ichi

    2014-06-01

    Auxin is a fundamental plant hormone and its localization within organs plays pivotal roles in plant growth and development. Analysis of many Arabidopsis mutants that were defective in auxin biosynthesis revealed that the indole-3-pyruvic acid (IPA) pathway, catalyzed by the TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA) and YUCCA (YUC) families, is the major biosynthetic pathway of indole-3-acetic acid (IAA). In contrast, little information is known about the molecular mechanisms of auxin biosynthesis in rice. In this study, we identified a auxin-related rice mutant, fish bone (fib). FIB encodes an orthologue of TAA genes and loss of FIB function resulted in pleiotropic abnormal phenotypes, such as small leaves with large lamina joint angles, abnormal vascular development, small panicles, abnormal organ identity and defects in root development, together with a reduction in internal IAA levels. Moreover, we found that auxin sensitivity and polar transport activity were altered in the fib mutant. From these results, we suggest that FIB plays a pivotal role in IAA biosynthesis in rice and that auxin biosynthesis, transport and sensitivity are closely interrelated.

  16. The rice FISH BONE gene encodes a tryptophan aminotransferase, which affects pleiotropic auxin-related processes.

    PubMed

    Yoshikawa, Takanori; Ito, Momoyo; Sumikura, Tsuyoshi; Nakayama, Akira; Nishimura, Takeshi; Kitano, Hidemi; Yamaguchi, Isomaro; Koshiba, Tomokazu; Hibara, Ken-Ichiro; Nagato, Yasuo; Itoh, Jun-Ichi

    2014-06-01

    Auxin is a fundamental plant hormone and its localization within organs plays pivotal roles in plant growth and development. Analysis of many Arabidopsis mutants that were defective in auxin biosynthesis revealed that the indole-3-pyruvic acid (IPA) pathway, catalyzed by the TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA) and YUCCA (YUC) families, is the major biosynthetic pathway of indole-3-acetic acid (IAA). In contrast, little information is known about the molecular mechanisms of auxin biosynthesis in rice. In this study, we identified a auxin-related rice mutant, fish bone (fib). FIB encodes an orthologue of TAA genes and loss of FIB function resulted in pleiotropic abnormal phenotypes, such as small leaves with large lamina joint angles, abnormal vascular development, small panicles, abnormal organ identity and defects in root development, together with a reduction in internal IAA levels. Moreover, we found that auxin sensitivity and polar transport activity were altered in the fib mutant. From these results, we suggest that FIB plays a pivotal role in IAA biosynthesis in rice and that auxin biosynthesis, transport and sensitivity are closely interrelated. PMID:24654985

  17. Bone metabolism of male rats chronically exposed to cadmium.

    PubMed

    Brzóska, Malgorzata M; Moniuszko-Jakoniuk, Janina

    2005-09-15

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females.

  18. Bone disease in hypoparathyroidism.

    PubMed

    Clarke, Bart L

    2014-07-01

    Hypoparathyroidism is a rare disorder that may be acquired or inherited. Postsurgical hypoparathyroidism is responsible for the majority of acquired hypoparathyroidism. Bone disease occurs in hypoparathyroidism due to markedly reduced bone remodeling due to the absence or low levels of parathyroid hormone. Chronically reduced bone turnover in patients with hypoparathyroidism typically leads to higher bone mass than in age- and sex-matched controls. Whether this increased bone density reduces fracture risk is less certain, because while increased bone mineralization may be associated with increased brittleness of bone, this does not appear to be the case in hypoparathyroidism. Treatment of hypoparathyroidism with recombinant parathyroid hormone may reduce bone mineral density but simultaneously strengthen the mechanical properties of bone.

  19. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    SciTech Connect

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S. . E-mail: msshiao@vghtpe.gov.tw

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.

  20. Infant formula increases bone turnover favoring bone formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the first year of life, the major infant food choices have traditionally been breast milk (BM), cow's milk formula (MF), or soy formula (SF). Studies examining the effects of infant formula on early life skeletal development are extremely limited. We have enrolled 120 healthy 6-month-old infants ...

  1. Biomass turnover time in terrestrial ecosystems halved by land use

    NASA Astrophysics Data System (ADS)

    Erb, Karl-Heinz; Fetzel, Tamara; Plutzar, Christoph; Kastner, Thomas; Lauk, Christian; Mayer, Andreas; Niedertscheider, Maria; Körner, Christian; Haberl, Helmut

    2016-09-01

    The terrestrial carbon cycle is not well quantified. Biomass turnover time is a crucial parameter in the global carbon cycle, and contributes to the feedback between the terrestrial carbon cycle and climate. Biomass turnover time varies substantially in time and space, but its determinants are not well known, making predictions of future global carbon cycle dynamics uncertain. Land use--the sum of activities that aim at enhancing terrestrial ecosystem services--alters plant growth and reduces biomass stocks, and is hence expected to affect biomass turnover. Here we explore land-use-induced alterations of biomass turnover at the global scale by comparing the biomass turnover of the actual vegetation with that of a hypothetical vegetation state with no land use under current climate conditions. We find that, in the global average, biomass turnover is 1.9 times faster with land use. This acceleration affects all biomes roughly equally, but with large differences between land-use types. Land conversion, for example from forests to agricultural fields, is responsible for 59% of the acceleration; the use of forests and natural grazing land accounts for 26% and 15% respectively. Reductions in biomass stocks are partly compensated by reductions in net primary productivity. We conclude that land use significantly and systematically affects the fundamental trade-off between carbon turnover and carbon stocks.

  2. Sex Affects Bone Morphogenetic Protein Type II Receptor Signaling in Pulmonary Artery Smooth Muscle Cells

    PubMed Central

    Mair, Kirsty M.; Yang, Xu Dong; Long, Lu; White, Kevin; Wallace, Emma; Ewart, Marie-Ann; Docherty, Craig K.; Morrell, Nicholas W.

    2015-01-01

    Rationale: Major pulmonary arterial hypertension (PAH) registries report a greater incidence of PAH in women; mutations in the bone morphogenic protein type II receptor (BMPR-II) occur in approximately 80% of patients with heritable PAH (hPAH). Objectives: We addressed the hypothesis that women may be predisposed to PAH due to normally reduced basal BMPR-II signaling in human pulmonary artery smooth muscle cells (hPASMCs). Methods: We examined the BMPR-II signaling pathway in hPASMCs derived from men and women with no underlying cardiovascular disease (non-PAH hPASMCs). We also determined the development of pulmonary hypertension in male and female mice deficient in Smad1. Measurements and Main Results: Platelet-derived growth factor, estrogen, and serotonin induced proliferation only in non-PAH female hPASMCs. Female non-PAH hPASMCs exhibited reduced messenger RNA and protein expression of BMPR-II, the signaling intermediary Smad1, and the downstream genes, inhibitors of DNA binding proteins, Id1 and Id3. Induction of phospho-Smad1/5/8 and Id protein by BMP4 was also reduced in female hPASMCs. BMP4 induced proliferation in female, but not male, hPASMCs. However, small interfering RNA silencing of Smad1 invoked proliferative responses to BMP4 in male hPASMCs. In male hPASMCs, estrogen decreased messenger RNA and protein expression of Id genes. The estrogen metabolite 4-hydroxyestradiol decreased phospho-Smad1/5/8 and Id expression in female hPASMCs while increasing these in males commensurate with a decreased proliferative effect in male hPASMCs. Female Smad1+/− mice developed pulmonary hypertension (reversed by ovariectomy). Conclusions: We conclude that estrogen-driven suppression of BMPR-II signaling in non-PAH hPASMCs derived from women contributes to a pro-proliferative phenotype in hPASMCs that may predispose women to PAH. PMID:25608111

  3. Perinatal maternal dietary supplementation of ω3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring.

    PubMed

    Fong, Laura; Muhlhausler, Beverly S; Gibson, Robert A; Xian, Cory J

    2012-05-01

    It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ω3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-κB ligand, TNF-α, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.

  4. Rapid Skeletal Turnover In A Radiographic Mimic Of Osteopetrosis

    PubMed Central

    Whyte, Michael P.; Madson, Katherine L.; Mumm, Steven; McAlister, William H.; Novack, Deborah V.; Blair, Jo C.; Helliwell, Timothy R.; Stolina, Marina; Abernethy, Laurence J.; Shaw, Nicholas J.

    2015-01-01

    Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis, and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was > 5,000 IU/L (normal < 850). After partial resection, the granuloma re-grew but then regressed and stabilized during three years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, BMD z-scores reached + 9.1 and + 5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of LRP4, LRP5, or TGFβ1 and for defective SOST, OPG, RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his non-consanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown. PMID:24919763

  5. THE IMMUNE SYSTEM AND BONE

    PubMed Central

    Pacifici, Roberto

    2010-01-01

    T cells and B cells produce large amounts of cytokines which regulate bone resorption and bone formation. These factors play a critical role in the regulation of bone turnover in health and disease. In addition, immune cells of the bone marrow regulate bone homeostasis by cross-talking with bone marrow stromal cells and osteoblastic cells via cell surface molecules. These regulatory mechanisms are particularly relevant for postmenopausal osteoporosis and hyperparathyroidism, two common forms of bone loss caused primarily by an expansion of the osteoclastic pool only partially compensated by a stimulation of bone formation. This article describes the cytokines and immune factors that regulate bone cells, the immune cells relevant to bone, examines the connection between T cells and bone in health and disease, and reviews the evidence in favor of a link between T cells and the mechanism of action of estrogen and PTH in bone. PMID:20599675

  6. The consequences of modern military deployment on calcium status and bone health.

    PubMed

    McCarthy, Mary S; Loan, Lori A; Azuero, Andres; Hobbs, Curtis

    2010-06-01

    This article highlights the potential negative effect of the current combat environment on bone health of young military men and women who may be at risk for stress fractures and future bone disease because of alterations primarily in diet and physical activity level during deployment. A combination of physiologic biomarkers, including bone turnover and bone mineral density, and nutrition and exercise surveys can provide meaningful data on potential health risks related to deployment. Soldiers participating in an investigation into bone health before and after deployment did not have decreased bone density but the study did raise awareness about an issue that might otherwise go unnoticed because preventive care is typically focused on older adults. Several risk factors may be modifiable and nurses have the necessary skills for counseling and monitoring behaviors that can minimize disabling musculoskeletal injuries that affect quality of life for the individual and unit readiness for the commander.

  7. Evaluation of a topical herbal agent for the promotion of bone healing.

    PubMed

    Siu, Wing-Sum; Ko, Chun-Hay; Lam, Ka-Wing; Wat, Elaine; Shum, Wai-Ting; Lau, Clara Bik-San; Ko, Kam-Ming; Hung, Leung-Kim; Lau, David Tai-Wai; Leung, Ping-Chung

    2015-01-01

    A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing. PMID:25810746

  8. Treatment with the combination of ibandronate plus eldecalcitol has a synergistic effect on inhibition of bone resorption without suppressing bone formation in ovariectomized rats.

    PubMed

    Sakai, Sadaoki; Takeda, Satoshi; Sugimoto, Masanori; Shimizu, Masaru; Shimonaka, Yasushi; Yogo, Kenji; Hashimoto, Junko; Bauss, Frieder; Endo, Koichi

    2015-12-01

    Bisphosphonates are widely used in the treatment of osteoporosis and contribute to the reduction of bone fractures. Ibandronate (IBN) is a highly potent, nitrogen-containing bisphosphonate, which is administered orally or intravenously at extended dosing intervals. Vitamin D or active vitamin D3 derivatives are also used in the treatment of osteoporosis, and are often used in combination with other drugs. In this study, we investigated the effect of treatment with the combination of once-monthly s.c. dosing of IBN plus once-daily oral eldecalcitol (ELD), an active vitamin D3 derivative, using aged ovariectomized (OVX) rats. Treatment was started the day after OVX, and analyses were performed 4, 8, and 12 weeks thereafter by determination of bone markers, bone mineral density, biomechanical properties, and histomorphometry. The combination treatment showed a synergistic effect in increasing both lumbar and femoral BMD, and resulted in a significant increase in bone ultimate load. The combination of IBN plus ELD acted synergistically to reduce bone resorption, whereas bone formation did not decrease any more than with monotherapy with either IBN or ELD. Bone formation independent of bone resorption (a process known as 'minimodeling') was not changed in vehicle treated OVX rats despite the increase in bone turnover. ELD upregulated minimodeling, which was however not diminished in the combination treatment. In conclusion, treatment with the combination of IBN plus ELD was beneficial in the treatment of osteoporosis in aged OVX rats. It exhibited a synergistic inhibitory effect on bone resorption and keeps bone formation at the level of sham controls. This uncoupling of bone resorption/bone formation was affected, to some extent, by minimodeling-based bone formation which is independent of bone resorption. This combination regimen which showed synergistic effect on BMD and bone ultimate load without inhibition of bone formation may be beneficial in long

  9. Does the Time of Postoperative Bisphosphonate Administration Affect the Bone Union in Osteoporotic Intertrochanteric Fracture of Femur?

    PubMed Central

    Cho, Yoon Je; Chun, Young Soo; Kang, Joon Soon; Jung, Gwang Young; Lee, Jun Hee

    2015-01-01

    Purpose This study was designed to investigate the effect of bisphosphonate administration starting time on bone healing and to identify the best administration time following surgical treatment of osteoporotic intertrochanteric fractures. Materials and Methods Two hundreds and eighty four patients (284 hips; 52 males, 232 females) who underwent surgery following osteoporotic intertrochanteric fracture from December 2002 to December 2012 were retrospectively analyzed. The average follow-up period was 68.4 months. The patients were divided into three groups according to the time of bisphosphonate administration after operation: 1 week (group A; n=102), 1 month (group B; n=89), and 3 months (group C; n=93). Koval scores and change of Koval scores 1 year after operation were used for clinical evaluation. For radiologic evaluation, the time of callus appearance across the fracture line on sagittal and coronal radiographs and the time to absence of pain during hip motion was judged as the time of bone union. Results Koval scores one year after surgery for groups A, B, and C were 2.44, 2.36, and 2.43 (P=0.895), respectively. The mean time of union was 12.4, 11.9, and 12.3 weeks after operation in the three groups (P=0.883), respectively. There were zero cases of nonunion. There were 3, 5, and 7 cases of fixative displacement in the three groups, respectively, but the distribution showed no significant difference (P>0.472). Conclusion The initiating time of bisphosphonate administration following surgery does not affect the clinical outcomes in patients with osteoporotic intertrochanteric fracture. PMID:27536634

  10. Repeated freeze-thaw cycles reduce the survival rate of osteocytes in bone-tendon constructs without affecting the mechanical properties of tendons.

    PubMed

    Suto, Kaori; Urabe, Ken; Naruse, Kouji; Uchida, Kentaro; Matsuura, Terumasa; Mikuni-Takagaki, Yuko; Suto, Mitsutoshi; Nemoto, Noriko; Kamiya, Kentaro; Itoman, Moritoshi

    2012-03-01

    Frozen bone-patellar tendon bone allografts are useful in anterior cruciate ligament reconstruction as the freezing procedure kills tissue cells, thereby reducing immunogenicity of the grafts. However, a small portion of cells in human femoral heads treated by standard bone-bank freezing procedures survive, thus limiting the effectiveness of allografts. Here, we characterized the survival rates and mechanisms of cells isolated from rat bones and tendons that were subjected to freeze-thaw treatments, and evaluated the influence of these treatments on the mechanical properties of tendons. After a single freeze-thaw cycle, most cells isolated from frozen bone appeared morphologically as osteocytes and expressed both osteoblast- and osteocyte-related genes. Transmission electron microscopic observation of frozen cells using freeze-substitution revealed that a small number of osteocytes maintained large nuclei with intact double membranes, indicating that these osteocytes in bone matrix were resistant to ice crystal formation. We found that tendon cells were completely killed by a single freeze-thaw cycle, whereas bone cells exhibited a relatively high survival rate, although survival was significantly reduced after three freeze-thaw cycles. In patella tendons, the ultimate stress, Young's modulus, and strain at failure showed no significant differences between untreated tendons and those subjected to five freeze-thaw cycles. In conclusion, we identified that cells surviving after freeze-thaw treatment of rat bones were predominantly osteocytes. We propose that repeated freeze-thaw cycles could be applied for processing bone-tendon constructs prior to grafting as the treatment did not affect the mechanical property of tendons and drastically reduced surviving osteocytes, thereby potentially decreasing allograft immunogenecity.

  11. Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

    PubMed

    Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

    2015-05-01

    The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

  12. Integrating Turnover Reasons and Shocks with Turnover Decision Processes

    ERIC Educational Resources Information Center

    Maertz, Carl P., Jr.; Kmitta, Kayla R.

    2012-01-01

    We interviewed and classified 186 quitters from many jobs and organizations via a theoretically-based protocol into five decision process types. We then tested exploratory hypotheses comparing users of these types on their propensity to report certain turnover reasons and turnover shocks. "Impulsive-type quitters," with neither a job offer in hand…

  13. Correlating the nanoscale mechanical and chemical properties of knockout mice bones

    NASA Astrophysics Data System (ADS)

    Kavukcuoglu, Nadire Beril

    Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2

  14. Bone remodeling during pregnancy and post-partum assessed by metal lead levels and isotopic concentrations.

    PubMed

    Gulson, Brian; Taylor, Alan; Eisman, John

    2016-08-01

    Bone remodeling is normally evaluated using bone turnover markers/indices as indicators of bone resorption and formation. However, during pregnancy and post-partum, there have been inconsistent results between and within biomarkers for bone formation and resorption. These differences may relate to pregnancy-related changes in metabolism and/or hemodilution altering measured marker levels. An alternative approach to evaluating bone remodeling is to use the metal lead (Pb) concentrations and Pb isotopic compositions in blood. These measurements can also provide information on the amount of Pb that is mobilized from the maternal skeleton. Despite some similarities with accepted bone turnover markers, the Pb data demonstrate increased bone resorption throughout pregnancy that further continues post-partum independent of length of breast-feeding, dietary intake and resumption of menses. Furthermore the isotopic measurements are not affected by hemodilution. These data confirm calcium balance studies that indicate increased bone resorption throughout pregnancy and lactation. They also indicate potentially major public health implications of the transfer of maternal Pb burden to the fetus and new born. PMID:27233973

  15. Factors affecting neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture

    PubMed Central

    Hoshino, Masatoshi; Terai, Hidetomi; Tsujio, Tadao; Nabeta, Masaharu; Namikawa, Takashi; Matsumura, Akira; Suzuki, Akinobu; Takayama, Kazushi; Takaoka, Kunio

    2009-01-01

    The purpose of this study was to examine factors affecting the severity of neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture (OVF). Reports of insufficient union following OVF have recently increased. Patients with this lesion have various degrees of neurological deficits and back pain. However, the factors contributing to the severity of these are still unknown. A total of 45 patients with insufficient union following OVF were included in this study. Insufficient union was diagnosed based on the findings of vertebral cleft on plain radiography or CT, as well as fluid collection indicating high-intensity change on T2-weighted MRI. Multivariate logistic regression analysis was performed to determine the factors contributing to the severity of neurological deficits and back pain in the patients. Age, sex, level of fracture, duration after onset of symptoms, degree of local kyphosis, degree of angular instability, ratio of occupation by bony fragments, presence or absence of protrusion of flavum, and presence or absence of ossification of the anterior longitudinal ligament (OALL) in the adjacent level were used as explanatory variables, while severity of neurological deficits and back pain were response variables. On multivariate analysis, factors significantly affecting the severity of neurological deficits were angular instability of more than 15° [adjusted odds ratio (OR), 9.24 (95% confidence interval, CI 1.49–57.2); P < 0.05] and ratio of occupation by bony fragments in the spinal canal of more than 42% [adjusted OR 9.23 (95%CI 1.15–74.1); P < 0.05]. The factor significantly affecting the severity of back pain was angular instability of more than 15° [adjusted OR 14.9 (95%CI 2.11–105); P < 0.01]. On the other hand, presence of OALL in the adjacent level reduced degree of back pain [adjusted OR 0.14 (95%CI 0.03–0.76); P < 0.05]. In this study, pronounced angular

  16. Disorders in bone metabolism of female rats chronically exposed to cadmium.

    PubMed

    Brzóska, Małgorzata M; Moniuszko-Jakoniuk, Janina

    2005-01-01

    The effect of cadmium (Cd) on bone metabolism during skeletal development and maturity was investigated on a rat model of human exposure. Young female Wistar rats were exposed to 1, 5, or 50 mg Cd/l in drinking water for 3, 6, 9, and 12 months. Total bone mineral density (T-BMD), bone mineral content (BMC), density (BMD), and bone area at the femur and lumbar spine (L1-L5) were measured densitometrically. Alkaline phosphatase (ALP) and osteocalcin (OC) as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in bone (trabecular and cortical) or serum as bone resorption markers were measured. Renal calcium (Ca) handling and Cd body burden were evaluated as well. At the stage of intensive skeletal development (the first 6 months of the experiment), at all exposure levels, Cd inhibited the processes of bone formation and as a result disturbed the accumulation of bone mass leading to osteopenia (- 1 > Z score/T score BMD > -2.5) and at 5 and 50 mg Cd/l even to more advanced disorders in the BMD. Continuation of the exposure up to skeletal maturity led to high bone turnover with increased resorption enhancing the prevalence of osteopenia or the BMD values having the Z score/T score < -2.5. The results allow for the conclusion that chronic, even low-level exposure to Cd disturbs bone metabolism during skeletal development and maturity by affecting bone turnover most probably through a direct influence on bone formation and resorption, and indirectly via disorders in Ca metabolism. Our findings confirm the hypothesis that environmental exposure to Cd may be a risk factor for low BMD.

  17. Breaking the turnover cycle.

    PubMed

    Nakhnikian, Elise

    2005-01-01

    The Paraprofessional Healthcare Institute, Bronx, NY, identifies seven elements which are essential for employers in their creation of a stable, well-qualified direct-care workforce. These "common sense" elements--ranging from paying family-sustaining wages to strengthening the caregiving relationship between the workers and those whom they serve--can make the difference between chronic turnover, on one hand, and employing a dedicated staff large enough to keep pace with the growing need for long-term care and services, on the other. However, implementing the seven elements requires the commitment, coordination, and the cooperation of the entire long-term care system, especially the state and federal reimbursement systems that pay for most care and services. By joining forces with other long-term care stakeholders, through organizations such as the Direct Care Alliance, providers can help stabilize the workforce and, ultimately, help to increase the allocation of public resources. PMID:16350897

  18. Do Non-collagenous Proteins Affect Skeletal Mechanical Properties?

    PubMed

    Morgan, Stacyann; Poundarik, Atharva A; Vashishth, Deepak

    2015-09-01

    The remarkable mechanical behavior of bone is attributed to its complex nanocomposite structure that, in addition to mineral and collagen, comprises a variety of non-collagenous matrix proteins or NCPs. Traditionally, NCPs have been studied as signaling molecules in biological processes including bone formation, resorption, and turnover. Limited attention has been given to their role in determining the mechanical properties of bone. Recent studies have highlighted that NCPs can indeed be lost or modified with aging, diseases, and drug therapies. Homozygous and heterozygous mice models of key NCP provide a useful approach to determine the impact of NCPs on bone morphology as well as matrix quality, and to carry out detailed mechanical analysis for elucidating the pathway by which NCPs can affect the mechanical properties of bone. In this article, we present a systematic analysis of a large cohort of NCPs on bone's structural and material hierarchy, and identify three principal pathways by which they determine bone's mechanical properties. These pathways include alterations of bone morphological parameters crucial for bone's structural competency, bone quality changes in key matrix parameters (mineral and collagen), and a direct role as load-bearing structural proteins.

  19. Textural and rheological properties of Pacific whiting surimi as affected by nano-scaled fish bone and heating rates.

    PubMed

    Yin, Tao; Park, Jae W

    2015-08-01

    Textural and rheological properties of Pacific whiting (PW) surimi were investigated at various heating rates with the use of nano-scaled fish bone (NFB) and calcium chloride. Addition of NFB and slow heating improved gel strength significantly. Activity of endogenous transglutaminase (ETGase) from PW surimi was markedly induced by both NFB calcium and calcium chloride, showing an optimal temperature at 30°C. Initial storage modulus increased as NFB calcium concentration increased and the same trend was maintained throughout the temperature sweep. Rheograms with temperature sweep at slow heating rate (1°C/min) exhibited two peaks at ∼ 35°C and ∼ 70°C. However, no peak was observed during temperature sweep from 20 to 90°C at fast heating rate (20°C/min). Protein patterns of surimi gels were affected by both heating rate and NFB calcium concentration. Under slow heating, myosin heavy chain intensity decreased with NFB calcium concentration, indicating formation of ε-(γ-glutamyl) lysine cross-links by ETGase and NFB calcium ion.

  20. Bone Adaptation and Regeneration - New Developments

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    Bone is a dynamic tissue that is constantly renewed and adapts to its local loading environment. Mechanical loading results in adaptive changes in bone size and shape that strengthen bone structure. The mechanisms for adaptation involve a multistep process called mechanotransduction, which is the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells. The transduction of a mechanical signal to a biochemical response involves pathways within the cell membrane and cytoskeleton of the osteocytes, the professional mechansensor cells of bone. During the last decade the role of mechanosensitive osteocytes in bone metabolism and turnover, and the lacuno-canalicular porosity as the structure that mediates mechanosensing, is likely to reveal a new paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Strain-derived fluid flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, as well as ensures transport of cell signaling molecules, nutrients and waste products. Cell-cell signaling from the osteocyte sensor cells to the effector cells (osteoblasts or osteoclasts), and the effector cell response - either bone formation or resorption, allow an explanation of local bone gain and loss as well as remodeling in response to fatigue damage as processes supervised by mechanosensitive osteocytes. The osteogenic activity of cultured bone cells has been quantitatively correlated with varying stress stimulations highlighting the importance of the rate of loading. Theoretically a possible mechanism for the stress response by osteocytes is due to strain amplification at the pericellular matrix. Single cell studies on molecular responses of osteocytes provide insight on local architectural alignment in bone during remodeling. Alignment seems to occur as a result of the

  1. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation

    PubMed Central

    Liu, Peng; Baumgart, Mario; Groth, Marco; Wittmann, Jürgen; Jäck, Hans-Martin; Platzer, Matthias; Tuckermann, Jan P.; Baschant, Ulrike

    2016-01-01

    Glucocorticoid-induced osteoporosis (GIO) is one of the major side effects of long-term glucocorticoid (GC) therapy mediated mainly via the suppression of bone formation and osteoblast differentiation independently of GC receptor (GR) dimerization. Since microRNAs play a critical role in osteoblast differentiation processes, we investigated the role of Dicer dependent microRNAs in the GC-induced suppression of osteoblast differentiation. MicroRNA sequencing of dexamethasone-treated wild-type and GR dimer-deficient mesenchymal stromal cells revealed GC-controlled miRNA expression in a GR dimer-dependent and GR dimer-independent manner. To determine the functional relevance of mature miRNAs in GC-induced osteoblast suppression, mice with an osteoblast-specific deletion of Dicer (DicerRunx2Cre) were exposed to glucocorticoids. In vitro generated Dicer-deficient osteoblasts were treated with dexamethasone and analyzed for proliferation, differentiation and mineralization capacity. In vivo, abrogation of Dicer-dependent miRNA biogenesis in osteoblasts led to growth retardation and impaired bone formation. However, subjecting these mice to GIO showed that bone formation was similar reduced in DicerRunx2Cre mice and littermate control mice upon GC treatment. In line, differentiation of Dicer deficient osteoblasts was suppressed to the same extent as wild type cells by GC treatment. Therefore, Dicer-dependent small RNA biogenesis in osteoblasts plays only a minor role in the pathogenesis of GC-induced inhibition of bone formation. PMID:27554624

  2. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation.

    PubMed

    Liu, Peng; Baumgart, Mario; Groth, Marco; Wittmann, Jürgen; Jäck, Hans-Martin; Platzer, Matthias; Tuckermann, Jan P; Baschant, Ulrike

    2016-01-01

    Glucocorticoid-induced osteoporosis (GIO) is one of the major side effects of long-term glucocorticoid (GC) therapy mediated mainly via the suppression of bone formation and osteoblast differentiation independently of GC receptor (GR) dimerization. Since microRNAs play a critical role in osteoblast differentiation processes, we investigated the role of Dicer dependent microRNAs in the GC-induced suppression of osteoblast differentiation. MicroRNA sequencing of dexamethasone-treated wild-type and GR dimer-deficient mesenchymal stromal cells revealed GC-controlled miRNA expression in a GR dimer-dependent and GR dimer-independent manner. To determine the functional relevance of mature miRNAs in GC-induced osteoblast suppression, mice with an osteoblast-specific deletion of Dicer (Dicer(Runx2Cre)) were exposed to glucocorticoids. In vitro generated Dicer-deficient osteoblasts were treated with dexamethasone and analyzed for proliferation, differentiation and mineralization capacity. In vivo, abrogation of Dicer-dependent miRNA biogenesis in osteoblasts led to growth retardation and impaired bone formation. However, subjecting these mice to GIO showed that bone formation was similar reduced in Dicer(Runx2Cre) mice and littermate control mice upon GC treatment. In line, differentiation of Dicer deficient osteoblasts was suppressed to the same extent as wild type cells by GC treatment. Therefore, Dicer-dependent small RNA biogenesis in osteoblasts plays only a minor role in the pathogenesis of GC-induced inhibition of bone formation. PMID:27554624

  3. [Clinical evaluation for abnormalities of bone and mineral metabolism in ESKD].

    PubMed

    Yano, Shozo

    2016-09-01

    In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD. PMID:27561341

  4. Autoradiographic imaging of phosphoinositide turnover in the brain

    SciTech Connect

    Hwang, P.M.; Bredt, D.S.; Snyder, S.H. )

    1990-08-17

    With ({sup 3}H)cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product ({sup 3}H)cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways.

  5. Prevalence of Bone Mineral Density Abnormalities and Factors Affecting Bone Density in Patients with Chronic Obstructive Pulmonary Disease in a Tertiary Care Hospital in Southern India

    PubMed Central

    Mani, Sathish Kumar; Gopal, Gopinath Kango; Rangasami, Srinivasan

    2016-01-01

    Introduction Chronic Obstructive Pulmonary Disease (COPD) is a disease of wasting with airflow limitation, associated with a variety of systemic manifestations such as reduced Bone Mineral Density (BMD). There is a paucity of Indian studies on the effects of COPD on BMD. Aim This study was conducted to estimate the prevalence of osteopenia and osteoporosis in COPD patients and the correlation between bone density and severity of COPD classified according to GOLD Global initiative for chronic Obstructive Lung Disease guidelines (GOLD). Materials and Methods A prospective study of 60 patients diagnosed to have COPD, was conducted in the outpatient department of Respiratory Medicine, at a tertiary care hospital in Southern India, between September 2012 and September 2013. BMD was measured using ultrasound bone densitometer (ACHILLES GE HEALTH CARE). Patients with a T-score between -1 and -2.5 were considered to be osteopenic while patients with a T score less than -2.5 were considered to be osteoporotic (WHO criteria). Results Overall, 40 (67%) patients had an abnormal bone mineral density. A total of 21 (35%) patients were osteoporotic while 19 (33%) were osteopenic. BMD levels correlated with severity of obstruction (p<0.001), smoking status (p=0.02), age (p=0.05) and number of pack years (p=0.001). Conclusion Patients with COPD are at an increased risk for lower BMD and osteoporotic fractures and the risk appears to increase with disease severity. Further studies are required to assess whether routine BMD measurements in COPD patients is beneficial to diagnose osteoporosis and reduce morbidity. PMID:27790490

  6. Treatment of subclinical hypothyroidism does not affect bone mass as determined by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women

    PubMed Central

    Roncero-Martin, Raul; Calderon-Garcia, Julian F.; Santos-Vivas, Mercedes; Vera, Vicente; Martínez-Alvárez, Mariana; Rey-Sanchez, Purificación

    2015-01-01

    Introduction The results of studies examining the influence of subclinical hypothyroidism (SCH) and levothyroxine (L-T4) replacement therapy on bone have generated considerable interest but also controversy. The present research aims to evaluate the effects of L-T4 treatment on different skeletal sites in women. Material and methods A group of 45 premenopausal (mean age: 43.62 ±6.65 years) and 180 postmenopausal (mean age: 59.51 ±7.90 years) women with SCH who were undergoing L-T4 replacement therapy for at least 6 months were compared to 58 pre- and 180 postmenopausal women with SCH (untreated) matched for age. The mean doses of L-T4 were 90.88 ±42.59 µg/day in the premenopausal women and 86.35 ±34.11 µg/day in the postmenopausal women. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual-energy X-ray absorptiometry (DXA) for the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm. Results No differences were observed between patients and untreated controls in these bone measurements except in the bone mineral density (BMD) of the spine (p = 0.0214) in postmenopausal women, which was greater in treated women than in untreated controls. Conclusions Our results indicate that adequate metabolic control through replacement treatment with L-T4 in pre- and postmenopausal women does not affect bone mass. PMID:26528344

  7. Dietary boron does not affect tooth strength, micro-hardness, and density, but affects tooth mineral composition and alveolar bone mineral density in rabbits fed a high-energy diet.

    PubMed

    Hakki, Sema S; SiddikMalkoc; Dundar, Niyazi; Kayis, Seyit Ali; Hakki, Erdogan E; Hamurcu, Mehmet; Baspinar, Nuri; Basoglu, Abdullah; Nielsen, Forrest H; Götz, Werner

    2015-01-01

    The objective of this study was to determine whether dietary boron (B) affects the strength, density and mineral composition of teeth and mineral density of alveolar bone in rabbits with apparent obesity induced by a high-energy diet. Sixty female, 8-month-old, New Zealand rabbits were randomly assigned for 7 months into five groups as follows: (1) control 1, fed alfalfa hay only (5.91 MJ/kg and 57.5 mg B/kg); (2) control 2, high energy diet (11.76 MJ and 3.88 mg B/kg); (3) B10, high energy diet + 10 mg B gavage/kg body weight/96 h; (4) B30, high energy diet + 30 mg B gavage/kg body weight/96 h; (5) B50, high energy diet + 50 mg B gavage/kg body weight/96 h. Maxillary incisor teeth of the rabbits were evaluated for compression strength, mineral composition, and micro-hardness. Enamel, dentin, cementum and pulp tissue were examined histologically. Mineral densities of the incisor teeth and surrounding alveolar bone were determined by using micro-CT. When compared to controls, the different boron treatments did not significantly affect compression strength, and micro-hardness of the teeth, although the B content of teeth increased in a dose-dependent manner. Compared to control 1, B50 teeth had decreased phosphorus (P) concentrations. Histological examination revealed that teeth structure (shape and thickness of the enamel, dentin, cementum and pulp) was similar in the B-treated and control rabbits. Micro CT evaluation revealed greater alveolar bone mineral density in B10 and B30 groups than in controls. Alveolar bone density of the B50 group was not different than the controls. Although the B treatments did not affect teeth structure, strength, mineral density and micro-hardness, increasing B intake altered the mineral composition of teeth, and, in moderate amounts, had beneficial effects on surrounding alveolar bone.

  8. The role of pleiotropy and linkage in genes affecting a sexual ornament and bone allocation in the chicken.

    PubMed

    Johnsson, M; Rubin, C-J; Höglund, A; Sahlqvist, A-S; Jonsson, K B; Kerje, S; Ekwall, O; Kämpe, O; Andersson, L; Jensen, P; Wright, D

    2014-05-01

    Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits. PMID:24655072

  9. The role of pleiotropy and linkage in genes affecting a sexual ornament and bone allocation in the chicken.

    PubMed

    Johnsson, M; Rubin, C-J; Höglund, A; Sahlqvist, A-S; Jonsson, K B; Kerje, S; Ekwall, O; Kämpe, O; Andersson, L; Jensen, P; Wright, D

    2014-05-01

    Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits.

  10. Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral

    PubMed Central

    Paschalis, E.P.; Tatakis, D.N.; Robins, S.; Fratzl, P.; Manjubala, I.; Zoehrer, R.; Gamsjaeger, S.; Buchinger, B.; Roschger, A.; Phipps, R.; Boskey, A.L.; Dall'Ara, E.; Varga, P.; Zysset, P.; Klaushofer, K.; Roschger, P.

    2011-01-01

    In the present study a rat animal model of lathyrism was employed to decipher whether anatomically confined alterations in collagen cross-links are sufficient to influence the mechanical properties of whole bone. Animal experiments were performed under an ethics committee approved protocol. Sixty-four female (47 day old) rats of equivalent weights were divided into four groups (16 per group): Controls were fed a semi-synthetic diet containing 0.6% calcium and 0.6% phosphorus for 2 or 4 weeks and β-APN treated animals were fed additionally with β-aminopropionitrile (0.1% dry weight). At the end of this period the rats in the four groups were sacrificed, and L2–L6 vertebra were collected. Collagen cross-links were determined by both biochemical and spectroscopic (Fourier transform infrared imaging (FTIRI)) analyses. Mineral content and distribution (BMDD) were determined by quantitative backscattered electron imaging (qBEI), and mineral maturity/crystallinity by FTIRI techniques. Micro-CT was used to describe the architectural properties. Mechanical performance of whole bone as well as of bone matrix material was tested by vertebral compression tests and by nano-indentation, respectively. The data of the present study indicate that β-APN treatment changed whole vertebra properties compared to non-treated rats, including collagen cross-links pattern, trabecular bone volume to tissue ratio and trabecular thickness, which were all decreased (p < 0.05). Further, compression tests revealed a significant negative impact of β-APN treatment on maximal force to failure and energy to failure, while stiffness was not influenced. Bone mineral density distribution (BMDD) was not altered either. At the material level, β-APN treated rats exhibited increased Pyd/Divalent cross-link ratios in areas confined to a newly formed bone. Moreover, nano-indentation experiments showed that the E-modulus and hardness were reduced only in newly formed bone areas under the influence

  11. Turnover of soil monosaccharides: Recycling versus Stabilization

    NASA Astrophysics Data System (ADS)

    Basler, Anna; Dyckmans, Jens

    2014-05-01

    Soil organic matter (SOM) represents a mixture of differently degradable compounds. Each of these compounds are characterised by different dynamics due to different chemical recalcitrance, transformation or stabilisation processes in soil. Carbohydrates represent one of these compounds and contribute up to 25 % to the soil organic matter. Vascular plants are the main source of pentose sugars (Arabinose and Xylose), whereas hexoses (Galactose and Mannose) are primarily produced by microorganisms. Several studies suggest that the mean turnover times of the carbon in soil sugars are similar to the turnover dynamics of the bulk carbon in soil. The aim of the study is to characterise the influence of stabilisation and turnover of soil carbohydrates. Soil samples are collected from (i) a continuous maize cropping experiment ('Höhere Landbauschule' Rotthalmünster, Bavaria) established 1979 on a Stagnic Luvisol and (ii) from a continuous wheat cropping, established 1969, as reference site. The effect of stabilisation is estimated by the comparison of turnover times of microbial and plant derived soil carbohydrates. As the dynamics of plant derived carbohydrate are solely influenced by stabilisation processes, whereas the dynamics of microbial derived carbohydrates are affected by recycling of organic carbon compounds derived by C3 plant substrate as well as stabilisation processes. The compound specific isotopic analysis (CSIA) of soil carbohydrates was performed using a HPLC/o/IRMS system. The chromatographic and mass spectrometric subunits were coupled with a LC-Isolink interface. Soil sugars were extracted after mild hydrolysis using 4 M trifluoroacetic acid (TFA). Chromatographic separation of the sugars was achieved using a low strength 0.25 mM NaOH solution as mobile phase at a ?ow rate of 250 μL min-1 at 10 ° C.

  12. Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

    NASA Technical Reports Server (NTRS)

    Cann, Christopher; Young, Donald R.

    1976-01-01

    Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

  13. Osteoarthritis and bone mineral density: are strong bones bad for joints?

    PubMed

    Hardcastle, Sarah A; Dieppe, Paul; Gregson, Celia L; Davey Smith, George; Tobias, Jon H

    2015-01-01

    Osteoarthritis (OA) is a common and disabling joint disorder affecting millions of people worldwide. In OA, pathological changes are seen in all of the joint tissues including bone. Although both cross-sectional and longitudinal epidemiological studies have consistently demonstrated an association between higher bone mineral density (BMD) and OA, suggesting that increased BMD is a risk factor for OA, the mechanisms underlying this observation remain unclear. Recently, novel approaches to examining the BMD-OA relationship have included studying the disease in individuals with extreme high bone mass, and analyses searching for genetic variants associated with both BMD variation and OA, suggesting possible pleiotropic effects on bone mass and OA risk. These studies have yielded valuable insights into potentially relevant pathways that might one day be exploited therapeutically. Although animal models have suggested that drugs reducing bone turnover (antiresorptives) may retard OA progression, it remains to be seen whether this approach will prove to be useful in human OA. Identifying individuals with a phenotype of OA predominantly driven by increased bone formation could help improve the overall response to these treatments. This review aims to summarise current knowledge regarding the complex relationship between BMD and OA.

  14. Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

    PubMed

    Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

    2014-01-01

    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck

  15. Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

    PubMed Central

    Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

    2014-01-01

    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore

  16. [Many issues about bone quality].

    PubMed

    Saito, Mitsuru

    2012-06-01

    According to the present definition of osteoporosis, bone mineral density, architecture, and tissue material properties are important factors in determining bone strength. Bone matrix consists of a two-phase composite material in which the mineral phase provides stiffness and collagen provide tensile strength and ductility. The proposed determinants of bone strength at the material level are the degree of mineralization of basic structure units, microdamage accumulation, and collagen cross-link formation. These are regulated by cellular activities, tissue turnover rate, and the levels of oxidative stress and glycation. In this review, I describe the concerns regarding bone qualities. PMID:22653026

  17. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  18. Current socio-economic measures, and not those measured during infancy, affect bone mass in poor urban South african children.

    PubMed

    Norris, Shane A; Sheppard, Zoë A; Griffiths, Paula L; Cameron, Noël; Pettifor, John M

    2008-09-01

    Understanding the impact of socio-economic status (SES) on physical development in children is important, especially in developing countries where considerable inequalities persist. This is the first study to examine the association between SES on bone development at the whole body, femoral neck, and lumbar spine in black children living in Soweto and Johannesburg, South Africa. Linear regression models were used to study associations between SES during infancy and current SES, anthropometric, and DXA-derived bone mass in 9/10-yr-old children (n = 309). Findings suggest that current SES measures, rather than SES during infancy, are stronger predictors of current whole body bone area (BA) and whole body BMC after adjusting for body size, pubertal development, physical activity, habitual dietary calcium intake, and body composition. SES had no significant effect on either hip or spine bone mass. Caregiver's marital/cohabiting status (indicator of social support) and whether there was a television in the home (indicator of greater income) at age 9/10 yr were the most important socio-economic determinants of whole body BA and BMC. SES has a significant independent effect on whole body BMC through its impact on BA. This suggests that poverty alleviation policies in South Africa could have a positive effect on bone health.

  19. Bone loss in chronic kidney disease: Quantity or quality?

    PubMed

    Zheng, Cai-Mei; Zheng, Jin-Quan; Wu, Chia-Chao; Lu, Chien-Lin; Shyu, Jia-Fwu; Yung-Ho, Hsu; Wu, Mei-Yi; Chiu, I-Jen; Wang, Yuan-Hung; Lin, Yuh-Feng; Lu, Kuo-Cheng

    2016-06-01

    Chronic kidney disease (CKD) patients experience bone loss and fracture because of a specific CKD-related systemic disorder known as CKD-mineral bone disorder (CKD-MBD). The bone turnover, mineralization, and volume (TMV) system describes the morphological bone lesions in renal osteodystrophy related to CKD-MBD. Bone turnover and bone volume are defined as high, normal, or low, and bone mineralization is classified as normal or abnormal. All types of bone histology related to TMV are responsible for both bone quantity and bone quality losses in CKD patients. This review focuses on current bone quantity and bone quality losses in CKD patients and finally discusses potential therapeutic measures. PMID:27049042

  20. Bone changes of mucolipidosis II at different ages. Postmortem study of three cases.

    PubMed

    Pazzaglia, U E; Beluffi, G; Castello, A; Coci, A; Zatti, G

    1992-03-01

    Bone changes are a constant feature of mucolipidosis II, with striking differences between newborns and older children. Intracellular, membrane-bound vacuoles were found in the chondrocytes, osteoblasts, osteocytes, and stromal fibroblasts of three affected children. Osteoclasts and marrow cells were unaffected. Ricketslike lesions were present at birth in the two younger cases, whereas signs of high bone turnover and defective calcification were no longer present in the older child. Severe abnormalities of the metaphyseal plate with the loss of normal cartilage architecture and the absence of endochondral ossification were the major changes in this age group.

  1. Current options for the treatment of Paget’s disease of the bone

    PubMed Central

    Merlotti, Daniela; Gennari, Luigi; Martini, Giuseppe; Nuti, Ranuccio

    2009-01-01

    Paget’s disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP) activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.

  2. The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture.

    PubMed

    Abbassy, Mona A; Watari, Ippei; Soma, Kunimichi

    2010-08-01

    The aim of this study was to assess the effect of type 1 diabetes mellitus (DM) on the structure of mandibular bone and on the changes of alveolar/jaw bone formation. Experimental DM was induced in 3-wk-old male Wistar rats by a single dose of 60 mg/kg body weight of streptozotocin. All rats were injected with calcein on days 21 and 28. The rats were killed when 8 wk of age. Bone structure was analyzed by bone histomorphometry, microcomputed tomography (micro-CT), and histological section. Histomorphometric analysis showed that the mineral apposition and the bone formation rates in most of the mandibular regions were significantly decreased in the DM group compared with the control group. Micro-CT analysis showed significant deterioration of the bone quality in rats with DM. For a histometric measure of bone resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The number of osteoclasts was significantly lower in the rats with DM than in the controls. These findings suggest that uncontrolled DM decreases mandibular bone formation, reduces the rate of bone turnover in the alveolar wall surrounding the root, and affects the quality of bone structure resulting in retardation of its skeletal development.

  3. Biomarkers of bone health and osteoporosis risk.

    PubMed

    Eastell, Richard; Hannon, Rosemary A

    2008-05-01

    The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N- and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in post-menopausal women and can also be used to assess the risk of fractures. In osteoporosis-treatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.

  4. Excess dietary methionine does not affect fracture healing in mice

    PubMed Central

    Holstein, Joerg H.; Schmalenbach, Julia; Herrmann, Markus; Ölkü, Ilona; Garcia, Patric; Histing, Tina; Herrmann, Wolfgang; Menger, Michael D.; Pohlemann, Tim; Claes, Lutz

    2012-01-01

    Summary Background An elevated serum concentration of homocysteine (hyperhomocysteinemia) has been shown to disturb fracture healing. As the essential amino acid, methionine, is a precursor of homocysteine, we aimed to investigate whether excess methionine intake affects bone repair. Material/Methods We analyzed bone repair in 2 groups of mice. One group was fed a methionine-rich diet (n=13), and the second group received an equicaloric control diet without methionine supplementation (n=12). Using a closed femoral fracture model, bone repair was analyzed by histomorphometry and biomechanical testing at 4 weeks after fracture. Blood was sampled to measure serum concentrations of homocysteine, the bone formation marker osteocalcin, and the bone resorption marker collagen I C-terminal crosslaps Results Serum concentrations of homocysteine were significantly higher in the methionine group than in the control group, while serum markers of bone turnover did not differ significantly between the 2 groups. Histomorphometry revealed no significant differences in size and tissue composition of the callus between animals fed the methionine-enriched diet and those receiving the control diet. Accordingly, animals of the 2 groups showed a comparable bending stiffness of the healing bones. Conclusions We conclude that excess methionine intake causes hyperhomocysteinemia, but does not affect fracture healing in mice. PMID:23197225

  5. Is bone mineral density measurement using dual-energy X-ray absorptiometry affected by gamma rays?

    PubMed

    Xie, Liang-Jun; Li, Jian-Fang; Zeng, Feng-Wei; Jiang, Hang; Cheng, Mu-Hua; Chen, Yi

    2013-01-01

    The objective of this study was to determine whether the gamma rays emitted from the radionuclide effect bone mineral density (BMD) measurement. Nine subjects (mean age: 56 ± 17.96 yr) scheduled for bone scanning underwent BMD measurement using dual-energy X-ray absorptiometry (DXA) (Hologic/Discovery A) before and 1, 2, and 4 h after injection of technetium-99m-methylene diphosphonate (99mTc-MDP). Ten subjects (mean age: 41 ± 15.47 yr) scheduled for therapy of differentiated thyroid carcinoma with iodine-131 underwent BMD measurement before and 2 h after therapeutic radionuclide administration. All patients were given whole body BMD measurement, including head, arm, ribs, lumbar spine, pelvis, and leg sites. Besides, patients who referred to radioiodine therapy were given total hip and femoral neck BMD measurement as well. No statistically significant changes in BMD values were detected after 99mTc-MDP and iodine-131 administration for all measurement sites (p > 0.05), and individual difference of BMD before and after radionuclide imaging or therapy was less than the least significant change in lumbar spine, total hip, and femoral neck. In conclusion, BMD measurements are not influenced by the gamma rays emitted from technetium-99m and iodine-131. DXA bone densitometry may be performed simultaneously with bone scanning and radioiodine therapy.

  6. Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis.

    PubMed

    Di Munno, O; Delle Sedie, A; Rossini, M; Adami, S

    2005-01-01

    This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).

  7. Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

    PubMed

    Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J; Freeman, Theresa A

    2016-09-01

    The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27510797

  8. Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Kogut, Michael H; Wolfenden, Amanda; Hernandez-Velasco, Xochitl; Hargis, Billy M; Bottje, Walter G; Bielke, Lisa R; Faulkner, Olivia B

    2014-01-01

    Two independent trials were conducted to evaluate the utilization of rye as energy source on bacterial translocation (BT), intestinal viscosity, gut integrity, gut microbiota composition, and bone mineralization, when compared with a traditional cereal (corn) in broiler chickens. In each experiment, day-of-hatch, broiler chickens were randomly assigned to either a corn or a rye diet (n = 20 chickens/group). At 10 d of age, in both experiments, 12 chickens/group were randomly selected, and given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood samples were collected to determine the passage of FITC-d. The liver was collected from each bird to evaluate BT. Duodenum, ileum, and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with rye showed increased (p < 0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that chickens fed with rye had increased the number of total lactic acid bacteria in all three sections of the gastrointestinal tract evaluated when compared to chickens fed with corn. Chickens fed with rye also had significantly higher coliforms in duodenum and ileum, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in chickens fed with rye when compared with corn fed chickens. In conclusion, rye evoked mucosal damage in chickens that alter the intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition as well as bone mineralization. Studies to evaluate dietary inclusion of selected DFM candidates that produce exogenous enzymes in rye fed chickens are currently being evaluated.

  9. Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

    PubMed

    Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J; Freeman, Theresa A

    2016-09-01

    The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Transformational leadership moderates the relationship between emotional exhaustion and turnover intention among community mental health providers.

    PubMed

    Green, Amy E; Miller, Elizabeth A; Aarons, Gregory A

    2013-08-01

    Public sector mental health care providers are at high risk for burnout and emotional exhaustion which negatively affect job performance and client satisfaction with services. Few studies have examined ways to reduce these associations, but transformational leadership may have a positive effect. We examine the relationships between transformational leadership, emotional exhaustion, and turnover intention in a sample of 388 community mental health providers. Emotional exhaustion was positively related to turnover intention, and transformational leadership was negatively related to both emotional exhaustion and turnover intention. Transformational leadership moderated the relationship between emotional exhaustion and turnover intention, indicating that having a transformational leader may buffer the effects of providers' emotional exhaustion on turnover intention. Investing in transformational leadership development for supervisors could reduce emotional exhaustion and turnover among public sector mental health providers.

  11. When and how is job embeddedness predictive of turnover? a meta-analytic investigation.

    PubMed

    Jiang, Kaifeng; Liu, Dong; McKay, Patrick F; Lee, Thomas W; Mitchell, Terence R

    2012-09-01

    The present meta-analytic study introduces an overall model of the relationships between job embeddedness and turnover outcomes. Drawing on 65 independent samples (N = 42,907), we found that on-the-job and off-the-job embeddedness negatively related to turnover intentions and actual turnover, after controlling for job satisfaction, affective commitment, and job alternatives. In addition, the negative relationships between on-the-job embeddedness (off-the-job embeddedness) and turnover criteria were stronger in female-dominated samples and public organizations (collectivistic countries). Finally, turnover intentions, job search behavior, and job performance fully (partially) mediated the effect of on-the-job embeddedness (off-the-job embeddedness) on actual turnover. The research and practical implications of our findings are noted, in light of study limitations and future research needs. PMID:22663557

  12. Transformational leadership moderates the relationship between emotional exhaustion and turnover intention among community mental health providers.

    PubMed

    Green, Amy E; Miller, Elizabeth A; Aarons, Gregory A

    2013-08-01

    Public sector mental health care providers are at high risk for burnout and emotional exhaustion which negatively affect job performance and client satisfaction with services. Few studies have examined ways to reduce these associations, but transformational leadership may have a positive effect. We examine the relationships between transformational leadership, emotional exhaustion, and turnover intention in a sample of 388 community mental health providers. Emotional exhaustion was positively related to turnover intention, and transformational leadership was negatively related to both emotional exhaustion and turnover intention. Transformational leadership moderated the relationship between emotional exhaustion and turnover intention, indicating that having a transformational leader may buffer the effects of providers' emotional exhaustion on turnover intention. Investing in transformational leadership development for supervisors could reduce emotional exhaustion and turnover among public sector mental health providers. PMID:22052429

  13. Transformational Leadership Moderates the Relationship between Emotional Exhaustion and Turnover Intention among Community Mental Health Providers

    PubMed Central

    Green, Amy E.; Miller, Elizabeth A.; Aarons, Gregory A.

    2014-01-01

    Public sector mental health care providers are at high risk for burnout and emotional exhaustion which negatively affect job performance and client satisfaction with services. Few studies have examined ways to reduce these associations, but transformational leadership may have a positive effect. We examine the relationships between transformational leadership, emotional exhaustion, and turnover intention in a sample of 388 community mental health providers. Emotional exhaustion was positively related to turnover intention, and transformational leadership was negatively related to both emotional exhaustion and turnover intention. Transformational leadership moderated the relationship between emotional exhaustion and turnover intention, indicating that having a transformational leader may buffer the effects of providers’ emotional exhaustion on turnover intention. Investing in transformational leadership development for supervisors could reduce emotional exhaustion and turnover among public sector mental health providers. PMID:22052429

  14. Three-Component Commitment and Turnover: An Examination of Temporal Aspects

    ERIC Educational Resources Information Center

    Culpepper, Robert A.

    2011-01-01

    SEM (N = 182) was employed to examine implied temporal aspects of three-component commitment theory as they relate to turnover. Consistent with expectations, affective commitment predicted subsequent turnover in an immediate and relatively short interval of 4 months, but failed to do in a much longer but outlying interval of 5-12 months. Side bet…

  15. Teacher Turnover Impact on 1st-8th Grade Student Academic Achievement: A Correlational Study

    ERIC Educational Resources Information Center

    Reid, Johnnie M.

    2010-01-01

    The impact of schools and students not meeting academic achievement standards affects the community and the nation's future workforce. This paper examines many of the factors influencing achievement with special attention given to the facts of teacher turnover in the schools. Teacher turnover and the sad state of the academic achievement of…

  16. Gaucher disease: the role of the specialist on metabolic bone diseases.

    PubMed

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

  17. Gaucher disease: the role of the specialist on metabolic bone diseases

    PubMed Central

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

  18. Gaucher disease: the role of the specialist on metabolic bone diseases.

    PubMed

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

  19. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    PubMed Central

    Yardley, Denise A

    2016-01-01

    There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. PMID:27217795

  20. The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis

    PubMed Central

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Uklejewski, Ryszard; Novotny, Karel; Kanicky, Viktor; Frankowski, Marcin

    2015-01-01

    The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

  1. The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis.

    PubMed

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Uklejewski, Ryszard; Novotny, Karel; Kanicky, Viktor; Frankowski, Marcin

    2015-01-01

    The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

  2. The Effects of Turnover: What We Know about Teacher Attrition

    ERIC Educational Resources Information Center

    DeAngelis, Karen

    2012-01-01

    School business officials are likely to know better than anyone else about the financial costs to districts and schools associated with teacher attrition. Perhaps less well-known, though, is what else has been learned about this issue in recent years--information that may affect how one thinks about teacher turnover. Here is some of that research:…

  3. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth.

    PubMed

    Page, Jonathan M; Merkel, Alyssa R; Ruppender, Nazanin S; Guo, Ruijing; Dadwal, Ushashi C; Cannonier, Shellese; Basu, Sandip; Guelcher, Scott A; Sterling, Julie A

    2015-09-01

    The contents of this data in brief are related to the article titled "Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II". In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2), poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP.

  4. Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection.

    PubMed

    Beil, Frank Timo; Oheim, Ralf; Barvencik, Florian; Hissnauer, Tim N; Pestka, Jan M; Ignatius, Anita; Rueger, Johannes M; Schinke, Thorsten; Clarke, Iain J; Amling, Michael; Pogoda, Pia

    2012-08-01

    The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular-application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamo-pituitary disconnection (HPD + OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro-CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD-sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo-pituitary axis is required for activation of bone turnover.

  5. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    PubMed Central

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  6. Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study.

    PubMed

    Dempster, David W; Zhou, Hua; Recker, Robert R; Brown, Jacques P; Recknor, Christopher P; Lewiecki, E Michael; Miller, Paul D; Rao, Sudhaker D; Kendler, David L; Lindsay, Robert; Krege, John H; Alam, Jahangir; Taylor, Kathleen A; Janos, Boris; Ruff, Valerie A

    2016-04-01

    We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab.

  7. Estimating Teacher Turnover Costs: A Case Study

    ERIC Educational Resources Information Center

    Levy, Abigail Jurist; Joy, Lois; Ellis, Pamela; Jablonski, Erica; Karelitz, Tzur M.

    2012-01-01

    High teacher turnover in large U.S. cities is a critical issue for schools and districts, and the students they serve; but surprisingly little work has been done to develop methodologies and standards that districts and schools can use to make reliable estimates of turnover costs. Even less is known about how to detect variations in turnover costs…

  8. Measuring Staff Turnover in Nursing Homes

    ERIC Educational Resources Information Center

    Castle, Nicholas G.

    2006-01-01

    Purpose: In this study the levels of staff turnover reported in the nursing home literature (1990-2003) are reviewed, as well as the definitions of turnover used in these prior studies. With the use of primary data collected from 354 facilities, the study addresses the various degrees of bias that result, depending on how staff turnover is defined…

  9. Using Turnover as a Recruitment Strategy

    ERIC Educational Resources Information Center

    Duncan, Sandra

    2009-01-01

    Teacher turnover is notoriously high in the field of early childhood education with an estimated 33% of staff exiting the workplace each year. Turnover is costly. Not only do high levels of turnover negatively impact children's growth and development, it also erodes the program's economic stability and wherewithal to provide effective operations…

  10. How Teacher Turnover Harms Student Achievement

    ERIC Educational Resources Information Center

    Ronfeldt, Matthew; Loeb, Susanna; Wyckoff, James

    2013-01-01

    Researchers and policymakers often assume that teacher turnover harms student achievement, though recent studies suggest this may not be the case. Using a unique identification strategy that employs school-by-grade level turnover and two classes of fixed-effects models, this study estimates the effects of teacher turnover on over 850,000 New York…

  11. Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

    PubMed

    Oliveri, M B; Wittich, A; Mautalen, C; Chaperon, A; Kizlansky, A

    2000-09-01

    Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P < 0.02; 3.131 +/- 0.367 versus 3.339 +/- 0.386 g, P < 0.05, respectively). In conclusion, peripheral BMD and BMC were similar in children and young adults from Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further.

  12. Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners.

    PubMed

    Luria, Tal; Matsliah, Yinnon; Adir, Yochai; Josephy, Noam; Moran, Daniel S; Evans, Rachel K; Abramovich, Amir; Eliakim, Alon; Nemet, Dan

    2010-01-01

    Submariners taking part in prolonged missions are exposed to environmental factors that may adversely affect bone health. Among these, relatively high levels of CO(2), lack of sunlight exposure affecting vitamin D metabolism, limited physical activity, and altered dietary habits. The aims of this study were to examine the effect of a prolonged submersion (30 days) on changes in bone strength using quantitative bone speed of sound and in markers of bone metabolism that include bone turnover (BAP, PINP, TRAP5b, and CTx) and endocrine regulators (serum calcium, PTH, and 25[OH]D) in a group of 32 young healthy male submariners. The prolonged submersion led to increases in body weight and BMI and to a decrease in fitness level. There was a significant decrease in bone strength following the submersion. Speed of sound exhibited continued decline at 4 weeks after return to shore and returned to baseline levels at the 6-month follow-up. There was a significant increase in circulating calcium level. PTH and 25(OH)D levels decreased significantly. Significant decreases were observed in both TRAP5b and CTx levels, markers of bone resorption, as well as in N-terminal propeptide of type I collagen (PINP), a bone formation marker. Prolonged submersion led to a significant decrease in bone strength, accompanied by an overall decrease in bone metabolism. Bone strength was regained only 6 months after return to shore. Prevention and/or rehabilitation programs should be developed following periods of relative disuse even for young submariners. The effects of repeated prolonged submersions on bone health are yet to be determined. PMID:19882096

  13. Fat and Bone: An Odd Couple

    PubMed Central

    Kremer, Richard; Gilsanz, Vicente

    2016-01-01

    In this review, we will first discuss the concept of bone strength and introduce how fat at different locations, including the bone marrow, directly or indirectly regulates bone turnover. We will then review the current literature supporting the mechanistic relationship between marrow fat and bone and our understanding of the relationship between body fat, body weight, and bone with emphasis on its hormonal regulation. Finally, we will briefly discuss the importance and challenges of accurately measuring the fat compartments using non-invasive methods. This review highlights the complex relationship between fat and bone and how these new concepts will impact our diagnostic and therapeutic approaches in the very near future. PMID:27014187

  14. Do Non-Collagenous Proteins Affect Skeletal Mechanical Properties?

    PubMed Central

    Morgan, Stacyann; Poundarik, Atharva A.; Vashishth, Deepak

    2015-01-01

    The remarkable mechanical behavior of bone is attributed to its complex nanocomposite structure that, in addition to mineral and collagen, comprises a variety of non-collagenous matrix proteins or NCPs. Traditionally, NCPs have been studied as signaling molecules in biological processes including bone formation, resorption and turnover. Limited attention has been given to their role in determining the mechanical properties of bone. Recent studies have highlighted that NCPs can indeed be lost or modified with aging, diseases and drug therapies. Homozygous and heterozygous mice models of key NCP provide a useful approach to determine the impact of NCPs on bone morphology as well as matrix quality, and to carry out detailed mechanical analysis for elucidating the pathway by which NCPs can affect the mechanical properties of bone. In this article, we present a systematic analysis of a large cohort of NCPs on bone’s structural and material hierarchy, and identify three principal pathways by which they determine bone’s mechanical properties. These pathways include alterations of bone morphological parameters crucial for bone’s structural competency, bone quality changes in key matrix parameters (mineral and collagen), and a direct role as load bearing structural proteins. PMID:26048282

  15. Neridronic acid for the treatment of bone metabolic diseases.

    PubMed

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Adami, Silvano

    2009-10-01

    Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns (< 12 month old) and in adult patients. In Paget's disease of bone, 200 mg intravenous neridronic acid is associated with a 65% rate of full remission and a biochemical response (decrease of > 75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance. PMID:19761412

  16. Changes in Bone Metabolism in Young Castrated Male Rats

    PubMed Central

    Ryu, Seong-Jun; Ryu, Dal-Sung; Kim, Jong-Yeol; Park, Jeong-Yoon; Kim, Kyung-Hyun; Chin, Dong-Kyu; Kim, Keun-Su; Cho, Yong-Eun

    2016-01-01

    Purpose To determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats. Materials and Methods A total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans. Results Femoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change. Conclusion In young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field. PMID:27593866

  17. Bone Health in Childhood: Usefulness of Biochemical Biomarkers

    PubMed Central

    Eapen, E.; Grey, V.; Don-Wauchope, A.; Atkinson, S. A.

    2008-01-01

    Development of the human skeleton begins in early embryonic life and continues through childhood into early adulthood. The acquisition of peak bone mass during these vulnerable periods may impact on skeletal fragility in later adult years. Once the skeleton has reached maturity, bone remodelling continues with periodic replacement of old bone with new at the same location. Bone biomarkers are specifically derived biomarkers that reflect both formation by osteoblasts and resorption by osteoclasts. Children have significantly higher concentrations of bone biomarkers than adults due to both skeletal growth and rapid bone turnover during childhood and adolescence. Biochemical assessment of markers of bone turnover may be important in the diagnosis, prognosis and management of metabolic bone disease. This review will discuss the various serum bone markers used for assessing bone health and the factors that influence their utility.

  18. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

    PubMed

    Duncan, Emma L; Danoy, Patrick; Kemp, John P; Leo, Paul J; McCloskey, Eugene; Nicholson, Geoffrey C; Eastell, Richard; Prince, Richard L; Eisman, John A; Jones, Graeme; Sambrook, Philip N; Reid, Ian R; Dennison, Elaine M; Wark, John; Richards, J Brent; Uitterlinden, Andre G; Spector, Tim D; Esapa, Chris; Cox, Roger D; Brown, Steve D M; Thakker, Rajesh V; Addison, Kathryn A; Bradbury, Linda A; Center, Jacqueline R; Cooper, Cyrus; Cremin, Catherine; Estrada, Karol; Felsenberg, Dieter; Glüer, Claus-C; Hadler, Johanna; Henry, Margaret J; Hofman, Albert; Kotowicz, Mark A; Makovey, Joanna; Nguyen, Sing C; Nguyen, Tuan V; Pasco, Julie A; Pryce, Karena; Reid, David M; Rivadeneira, Fernando; Roux, Christian; Stefansson, Kari; Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Tichawangana, Rumbidzai; Evans, David M; Brown, Matthew A

    2011-04-01

    Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

  19. Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

    PubMed Central

    Duncan, Emma L.; Danoy, Patrick; Kemp, John P.; Leo, Paul J.; McCloskey, Eugene; Nicholson, Geoffrey C.; Eastell, Richard; Prince, Richard L.; Eisman, John A.; Jones, Graeme; Sambrook, Philip N.; Reid, Ian R.; Dennison, Elaine M.; Wark, John; Richards, J. Brent; Uitterlinden, Andre G.; Spector, Tim D.; Esapa, Chris; Cox, Roger D.; Brown, Steve D. M.; Thakker, Rajesh V.; Addison, Kathryn A.; Bradbury, Linda A.; Center, Jacqueline R.; Cooper, Cyrus; Cremin, Catherine; Estrada, Karol; Felsenberg, Dieter; Glüer, Claus-C.; Hadler, Johanna; Henry, Margaret J.; Hofman, Albert; Kotowicz, Mark A.; Makovey, Joanna; Nguyen, Sing C.; Nguyen, Tuan V.; Pasco, Julie A.; Pryce, Karena; Reid, David M.; Rivadeneira, Fernando; Roux, Christian; Stefansson, Kari; Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Tichawangana, Rumbidzai; Evans, David M.; Brown, Matthew A.

    2011-01-01

    Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. PMID:21533022

  20. Bone material properties in premenopausal women with idiopathic osteoporosis

    PubMed Central

    Misof, BM; Gamsjaeger, S; Cohen, A; Hofstetter, B; Roschger, P; Stein, E; Nickolas, TL; Rogers, HF; Dempster, D; Zhou, H; Recker, R; Lappe, J; McMahon, D; Paschalis, EP; Fratzl, P; Shane, E; Klaushofer, K

    2012-01-01

    Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content and collagen cross-link ratio at actively bone forming trabecular surfaces by Raman and Fourier Transform Infrared (FTIRM) microspectroscopic techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n=45), or idiopathic low BMD (Z-score ≤-2.0 at spine and/or hip) but no fractures (ILBMD, n=19), and healthy controls (CONTROL, n=38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both Cn.CaMean and Cn.CaPeak are 1.4% lower) and in ILBMD (both are 1.6% lower, p<0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls

  1. How does the supernatant of Lactobacillus acidophilus affect the proliferation and differentiation activities of rat bone marrow-derived stromal cells?

    PubMed

    Samadikuchaksaraei, A; Gholipourmalekabadi, M; Saberian, M; Abdollahpour Alitappeh, M; Shahidi Delshad, E

    2016-01-01

    Low proliferation rate and unwanted differentiation of bone marrow-derived stromal cells (rBMSCs) during the frequent passages have limited the use of such cells in clinical cell therapy. Recently, the researchers have focused on the effects of the components produced by some bacteria on proliferation of the stem cells. In this study, we discussed the possible effects of the Lactobacillus acidophilus supernatant on proliferation and differentiation of the rBMSCs. For this aim, the cells were isolated from rat bone marrow, characterized by culturing on tissue specific differentiation media and stained. The cells (passage two) were treated with different concentrations of the L. acidophilus supernatant (0, 0.1, 0.3, 0.9, 3, 9 and 30 &mgr;l/ml) for 14 days. The proliferation and differentiation capacity of the cells were then determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT assay) and tissue specific staining. The results showed a positive effect of the supernatant on the cell proliferation in 3 and 9 &mgr;l/ml concentrations, while did not affect the differentiation capacity of the rBMSCs. The current study strongly suggests the L. acidophilus supernatant as an alternative material that could be added to the media with aim of improvement in the proliferation rate of the rBMSCs without affecting their differentiation capacity. PMID:27609467

  2. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis

    PubMed Central

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J.

    2016-01-01

    Background Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. Material/Methods The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. Results While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. Conclusions Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  3. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis.

    PubMed

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J

    2016-01-01

    BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss. PMID:27550548

  4. New trends in bone research.

    PubMed

    Hewison, M

    1995-01-01

    Recent advances in bone research have employed novel cell and molecular biology techniques to determine some of the fundamental mechanisms regulating bone function. Endocrine control of bone cell development and matrix turnover have been defined at a molecular level by studying the interaction of steroid/thyroid hormones with gene promoters. New steroid/thyroid hormone receptors have been cloned, suggesting that our current view of hormonal regulation of bone metabolism is far from complete. The function of one particular steroid hormone receptor, the vitamin D receptor, has come under close scrutiny following the observation that polymorphic variations in this receptor are linked to differences in bone mineral density. Detailed studies of bone cell differentiation have shown that cytokines may be particularly important targets for hormonal control in bone. The role of cell adhesion molecules in regulating bone resorption has also been explored; modulation of their activity may be of benefit in the treatment of diseases such as osteoporosis. Pharmacological intervention via the newly cloned calcium-sensing receptor offers another site for regulation of bone turnover. PMID:8847678

  5. Growth Factor Content in Human Sera Affects the Isolation of Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

    PubMed Central

    Montali, Marina; Barachini, Serena; Panvini, Francesca M.; Carnicelli, Vittoria; Fulceri, Franca; Petrini, Iacopo; Pacini, Simone

    2016-01-01

    Mesangiogenic Progenitor Cells (MPCs) are human bone marrow-derived multipotent cells, isolated in vitro under selective culture conditions and shown to retain both mesengenic and angiogenic potential. MPCs also co-isolated with multipotent stromal cells (MSCs) when bone marrow primary cultures were set up for clinical applications, using human serum (HS) in place of fetal bovine serum (FBS). MPC culture purity (over 95%) is strictly dependent on HS supplementation with significant batch-to-batch variability. In the present paper we screened different sources of commercially available pooled human AB type serum (PhABS) for their ability to promote MPC production under selective culture conditions. As the majority of “contaminating” cells in MPC cultures were represented by MSC-like cells, we hypothesized a role by differentiating agents present in the sera. Therefore, we tested a number of growth factors (hGF) and found that higher concentrations of FGF-2, EGF, PDGF-AB, and VEGF-A as well as lower concentration of IGF-1 give sub-optimal MPC recovery. Gene expression analysis of hGF receptors was also carried out both in MSCs and MPCs, suggesting that FGF-2, EGF, and PDGF-AB could act promoting MSC proliferation, while VEGF-A contribute to MSC-like cell contamination, triggering MPC differentiation. Here we demonstrated that managing hGF contents, together with applying specific receptors inhibitors (Erlotinib-HCl and Nintedanib), could significantly mitigate the batch-to-batch variability related to serum supplementation. These data represent a fundamental milestone in view of manufacturing MPC-based medicinal products. PMID:27800477

  6. Reproductive hormones and bone.

    PubMed

    Nicks, Kristy M; Fowler, Tristan W; Gaddy, Dana

    2010-06-01

    Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates secretion of pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which directly regulate ovarian function. Pituitary FSH can modulate osteoclast development, and thereby influence bone turnover. Pituitary oxytocin and prolactin effects on the skeleton are not merely limited to pregnancy and lactation; oxytocin stimulates osteoblastogenesis and bone formation, whereas prolactin exerts skeletal effects in an age-dependent manner. Cyclic levels of inhibins and estrogen suppress FSH and LH, respectively, and also suppress bone turnover via their suppressive effects on osteoblast and osteoclast differentiation. However, continuous exposure to inhibins or estrogen/androgens is anabolic for the skeleton in intact animals and protects against gonadectomy-induced bone loss. Alterations of one hormone in the hypothalamic-pituitary-gonadal (HPG) axis influence other bone-active hormones in the entire feedback loop in the axis. Thus, we propose that the action of the HPG axis should be extended to include its combined effects on the skeleton, thus creating the HPG skeletal (HPGS) axis.

  7. Exercise frequency and bone mineral density development in exercising postmenopausal osteopenic women. Is there a critical dose of exercise for affecting bone? Results of the Erlangen Fitness and Osteoporosis Prevention Study.

    PubMed

    Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

    2016-08-01

    Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation.

  8. Exercise frequency and bone mineral density development in exercising postmenopausal osteopenic women. Is there a critical dose of exercise for affecting bone? Results of the Erlangen Fitness and Osteoporosis Prevention Study.

    PubMed

    Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

    2016-08-01

    Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation. PMID:27108341

  9. Bone and the immune system.

    PubMed

    Gruber, H E

    1991-07-01

    There are several lines of evidence which provide support for an important relationship between immune cells and bone. Clinical studies of immunodeficiency syndromes have shown that abnormalities in bone shape are evident on x-rays, and peculiarities in the structure of the growth plate have been identified by histopathology. Studies of bone histology, and quantitation of cellular abnormalities, are scarce. Abnormalities in bone turnover, have, however, been identified in the nude mouse model. Many lines of evidence derived from in vitro bone studies have shown that lymphokines and monokines can influence bone formation and bone resorption. Some clinical studies of postmenopausal osteoporosis have indicated the possible presence of immune cell changes in this condition. Although several hypotheses have been formed regarding the exact mechanisms of the effect of immune cytokine on bone, this is clearly a very large area of study and there is a need for additional carefully controlled experiments with special emphasis on bone cells and bone matrix, especially in the human. As knowledge progresses regarding immunology and hematology, a clearer understanding of the lineages of the osteoblast and osteoclast will emerge and we will better understand how specialized bone cells interact with and react to their immune cell neighbors in the bone marrow and to immune system signals. These findings will have especially important implications for the local bone loss seen in rheumatoid arthritis, periodontal disease, and chronic osteomyelitis. PMID:2068116

  10. Nicotine Affects Bone Resorption and Suppresses the Expression of Cathepsin K, MMP-9 and Vacuolar-Type H+-ATPase d2 and Actin Organization in Osteoclasts

    PubMed Central

    Tanaka, Hideki; Tanabe, Natsuko; Kawato, Takayuki; Nakai, Kumiko; Kariya, Taro; Matsumoto, Sakurako; Zhao, Ning; Motohashi, Masafumi; Maeno, Masao

    2013-01-01

    Tobacco smoking is an important risk factor for the development of several cancers, osteoporosis, and inflammatory diseases such as periodontitis. Nicotine is one of the major components of tobacco. In previous study, we showed that nicotine inhibits mineralized nodule formation by osteoblasts, and the culture medium from osteoblasts containing nicotine and lipopolysaccharide increases osteoclast differentiation. However, the direct effect of nicotine on the differentiation and function of osteoclasts is poorly understood. Thus, we examined the direct effects of nicotine on the expression of nicotine receptors and bone resorption-related enzymes, mineral resorption, actin organization, and bone resorption using RAW264.7 cells and bone marrow cells as osteoclast precursors. Cells were cultured with 10−5, 10−4, or 10−3 M nicotine and/or 50 µM α-bungarotoxin (btx), an 7 nicotine receptor antagonist, in differentiation medium containing the soluble RANKL for up 7 days. 1–5, 7, 9, and 10 nicotine receptors were expressed on RAW264.7 cells. The expression of 7 nicotine receptor was increased by the addition of nicotine. Nicotine suppressed the number of tartrate-resistant acid phosphatase positive multinuclear osteoclasts with large nuclei(≥10 nuclei), and decreased the planar area of each cell. Nicotine decreased expression of cathepsin K, MMP-9, and V-ATPase d2. Btx inhibited nicotine effects. Nicotine increased CA II expression although decreased the expression of V-ATPase d2 and the distribution of F-actin. Nicotine suppressed the planar area of resorption pit by osteoclasts, but did not affect mineral resorption. These results suggest that nicotine increased the number of osteoclasts with small nuclei, but suppressed the number of osteoclasts with large nuclei. Moreover, nicotine reduced the planar area of resorption pit by suppressing the number of osteoclasts with large nuclei, V-ATPase d2, cathepsin K and MMP-9 expression and actin organization. PMID

  11. The Steady-State Serum Concentration of Genistein Aglycone Is Affected by Formulation: A Bioequivalence Study of Bone Products

    PubMed Central

    Bitto, Alessandra; Burnett, Bruce P.; Polito, Francesca; Russo, Silvia; D'Anna, Rosario; Pillai, Lakshmi; Squadrito, Francesco; Altavilla, Domenica; Levy, Robert M.

    2013-01-01

    An FDA-regulated, prescription medical food (Fosteum; 27 mg natural genistein, 200 IU cholecalciferol, 20 mg citrated zinc bisglycinate (4 mg elemental zinc) per capsule) and an over-the-counter (OTC) supplement (Citracal Plus Bone Density Builder; 27 mg synthetic genistein, 600 mg elemental calcium (calcium citrate), 400 IU vitamin D3, 50 mg magnesium, 7.5 mg zinc, 1 mg copper, 75 μg molybdenum, 250 μg boron per two tablets) were compared to a clinically proven bone formulation (27 mg natural genistein, 400 IU cholecalciferol, 500 mg elemental calcium (calcium carbonate) per tablet; the Squadrito formulation) in an 8-day steady-state pharmacokinetic (PK) study of healthy postmenopausal women (n = 30) randomized to receive 54 mg of genistein per day. Trough serum samples were obtained before the final dose on the morning of the ninth day followed by sampling at 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hrs. Total serum genistein, after β-glucuronidase/sulfatase digestion, was measured by time-resolved fluorometric assay. Maximal time (Tmax), concentration (Cmax), half-life (T1/2), and area under the curve (AUC) were determined for genistein in each formulation. Fosteum and the Squadrito study formulation were equivalent for genistein Tmax (2 hrs), Cmax (0.7 μM), T1/2 (18 ± 6.9 versus 21 ± 4.9 hrs), and AUC (9221 ± 413 versus 9818 ± 1370 ng·hr/mL). The OTC supplement's synthetically derived genistein, however, showed altered Tmax (6 hrs), Cmax (0.57 μM), T1/2 (8.3 ± 1.9 hrs), and AUC (6474 ± 287 ng·hr/mL). Differences in uptake may be due to multiple ingredients in the OTC supplement which interfere with genistein absorption. PMID:23484100

  12. Methyl group turnover on methyl-accepting chemotaxis proteins during chemotaxis by Bacillus subtilis

    SciTech Connect

    Thoelke, M.S.; Casper, J.M.; Ordal, G.W. )

    1990-02-05

    The addition of attractant to Bacillus subtilis briefly exposed to radioactive methionine causes an increase of labeling of the methyl-accepting chemotaxis proteins. The addition of attractant to cells radiolabeled for longer times shows no change in the extent of methylation. Therefore, the increase in labeling for the briefly labeled cells is due to an increased turnover of methyl groups caused by attractant. All amino acids gave enhanced turnover. This turnover lasted for a prolonged time, probably spanning the period of smooth swimming caused by the attractant addition. Repellent did not affect the turnover when added alone or simultaneously with attractant. Thus, for amino acid attractants, the turnover is probably the excitatory signal, which is seen to extend long into or throughout the adaptation period, not just at the start of it.

  13. Bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation.

    PubMed

    Zhang, Yiran; Hu, Kaimin; Hu, Yongxian; Liu, Lizhen; Wang, Binsheng; Huang, He

    2014-09-01

    The effect of bone marrow microenvironment on the cell cycle of acute lymphocytic leukemia (ALL) and the underlying mechanism has not been elucidated. In this study, we found that in normal condition, bone marrow mesenchymal stromal cells (BM-MSCs) had no significant effect on the cell cycle and apoptosis of ALL; in the condition when the cell cycle of ALL was blocked by genotoxic agents, BM-MSCs could increase the S-phase cell ratio and decrease the G2/M phase ratio of ALL. Besides, BM-MSCs could protect ALL cells from drug-induced apoptosis. Then, we proved that BM-MSCs affect the cell cycle arrest effect of genotoxic agents on ALL cells via p21 down-regulation. Moreover, our results indicated that activation of Wnt/β-catenin and Erk pathways might be involved in the BM-MSC-induced down-regulation of p21 in ALL cells. Targeting microenvironment-related signaling pathway may therefore be a potential novel approach for ALL therapy.

  14. Basketball Affects Bone Mineral Density Accrual in Boys More Than Swimming and Other Impact Sports: 9-mo Follow-Up.

    PubMed

    Agostinete, Ricardo R; Lynch, Kyle R; Gobbo, Luís A; Lima, Manoel Carlos Spiguel; Ito, Igor H; Luiz-de-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Romulo A

    2016-01-01

    The objective of this study was to analyze the effect of different sports on bone mineral density (BMD) accrual among male adolescents during a 9-mo follow-up. The sample was composed of 82 boys (control [n = 13], basketball [n = 14], karate [n = 9], soccer [n = 18], judo [n = 12], and swimming [n = 16]) who were followed up for 9 mo (from October 2013 to August 2014). BMD (gram per square centimeter) was assessed at baseline and follow-up using a dual-energy X-ray absorptiometry scanner, whereas somatic maturation was estimated through the use of the peak height velocity. Vitamin D consumption was assessed by questionnaire. After 9 mo of follow-up, all groups (including the control group) presented significant BMD accrual (overall sample: 4.5% in the whole body). On the other hand, the basketball group presented higher BMD accrual in the upper limbs (17.6%) than the control group (7.2%). A similar difference was observed in whole-body BMD (control group: 4.1% vs basketball group: 7.1%). The basketball group had significantly higher BMD gains than the control group and other sports groups. PMID:27174316

  15. Basketball Affects Bone Mineral Density Accrual in Boys More Than Swimming and Other Impact Sports: 9-mo Follow-Up.

    PubMed

    Agostinete, Ricardo R; Lynch, Kyle R; Gobbo, Luís A; Lima, Manoel Carlos Spiguel; Ito, Igor H; Luiz-de-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Romulo A

    2016-01-01

    The objective of this study was to analyze the effect of different sports on bone mineral density (BMD) accrual among male adolescents during a 9-mo follow-up. The sample was composed of 82 boys (control [n = 13], basketball [n = 14], karate [n = 9], soccer [n = 18], judo [n = 12], and swimming [n = 16]) who were followed up for 9 mo (from October 2013 to August 2014). BMD (gram per square centimeter) was assessed at baseline and follow-up using a dual-energy X-ray absorptiometry scanner, whereas somatic maturation was estimated through the use of the peak height velocity. Vitamin D consumption was assessed by questionnaire. After 9 mo of follow-up, all groups (including the control group) presented significant BMD accrual (overall sample: 4.5% in the whole body). On the other hand, the basketball group presented higher BMD accrual in the upper limbs (17.6%) than the control group (7.2%). A similar difference was observed in whole-body BMD (control group: 4.1% vs basketball group: 7.1%). The basketball group had significantly higher BMD gains than the control group and other sports groups.

  16. Protein turnover, ureagenesis and gluconeogenesis.

    PubMed

    Schutz, Yves

    2011-03-01

    The major processes discussed below are protein turnover (degradation and synthesis), degradation into urea, or conversion into glucose (gluconeogenesis, Figure 1). Daily protein turnover is a dynamic process characterized by a double flux of amino acids: the amino acids released by endogenous (body) protein breakdown can be reutilized and reconverted to protein synthesis, with very little loss. Daily rates of protein turnover in humans (300 to 400 g per day) are largely in excess of the level of protein intake (50 to 80 g per day). A fast growing rate, as in premature babies or in children recovering from malnutrition, leads to a high protein turnover rate and a high protein and energy requirement. Protein metabolism (synthesis and breakdown) is an energy-requiring process, dependent upon endogenous ATP supply. The contribution made by whole-body protein turnover to the resting metabolic rate is important: it represents about 20 % in adults and more in growing children. Metabolism of proteins cannot be disconnected from that of energy since energy balance influences net protein utilization, and since protein intake has an important effect on postprandial thermogenesis - more important than that of fats or carbohydrates. The metabolic need for amino acids is essentially to maintain stores of endogenous tissue proteins within an appropriate range, allowing protein homeostasis to be maintained. Thanks to a dynamic, free amino acid pool, this demand for amino acids can be continuously supplied. The size of the free amino acid pool remains limited and is regulated within narrow limits. The supply of amino acids to cover physiological needs can be derived from 3 sources: 1. Exogenous proteins that release amino acids after digestion and absorption 2. Tissue protein breakdown during protein turnover 3. De novo synthesis, including amino acids (as well as ammonia) derived from the process of urea salvage, following hydrolysis and microflora metabolism in the hind gut

  17. Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages.

    PubMed

    Arya, Nlin; Moonarmart, Walasinee; Cheewamongkolnimit, Nareerat; Keratikul, Nutcha; Poon-Iam, Sawinee; Routh, Andrew; Bumpenpol, Pitikarn; Angkawanish, Taweepoke

    2015-11-01

    Bone turnover markers could offer a potential alternative means for the early diagnosis of metabolic bone disease in young growing elephants although the baseline of bone turnover markers in elephant is not well established. The aim of this study was to determine any relationship between the age of captive Asian elephants (Elephas maximus) and markers of bone formation. Serum samples from 24 female Asian elephants were collected to evaluate levels of two bone formation markers, namely, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Both intact and N-terminal midfragment OC and BAP were negatively correlated with age. The findings demonstrate that younger elephants have a higher rate of bone turnover than older elephants. Use of these and additional bone markers could lead to the establishment of validated protocols for the monitoring of bone disease in elephants. PMID:26361748

  18. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovariectomy (OVX)-induced bone loss has been linked to increased bone turnover and higher bone matrix collagen degradation as the result of osteoclast activation. However, the role of degraded collagen matrix in the fate of resident bone-forming cells is unclear. In this report, we show that OVX-i...

  19. Bisphosphonates and bone quality

    PubMed Central

    Pazianas, Michael; van der Geest, Stefan; Miller, Paul

    2014-01-01

    Bisphosphonates (BPs) are bone-avid compounds used as first-line medications for the prevention and treatment of osteoporosis. They are also used in other skeletal pathologies such as Paget's and metastatic bone disease. They effectively reduce osteoclast viability and also activity in the resorptive phase of bone remodelling and help preserve bone micro-architecture, both major determinants of bone strength and ultimately of the susceptibility to fractures. The chemically distinctive structure of each BP used in the clinic determines their unique affinity, distribution/penetration throughout the bone and their individual effects on bone geometry, micro-architecture and composition or what we call ‘bone quality'. BPs have no clinically significant anabolic effects. This review will touch upon some of the components of bone quality that could be affected by the administration of BPs. PMID:24876930

  20. Sex-chromosome turnovers induced by deleterious mutation load.

    PubMed

    Blaser, Olivier; Grossen, Christine; Neuenschwander, Samuel; Perrin, Nicolas

    2013-03-01

    In sharp contrast with mammals and birds, many cold-blooded vertebrates present homomorphic sex chromosomes. Empirical evidence supports a role for frequent turnovers, which replace nonrecombining sex chromosomes before they have time to decay. Three main mechanisms have been proposed for such turnovers, relying either on neutral processes, sex-ratio selection, or intrinsic benefits of the new sex-determining genes (due, e.g., to linkage with sexually antagonistic mutations). Here, we suggest an additional mechanism, arising from the load of deleterious mutations that accumulate on nonrecombining sex chromosomes. In the absence of dosage compensation, this load should progressively lower survival rate in the heterogametic sex. Turnovers should occur when this cost outweighs the benefits gained from any sexually antagonistic genes carried by the nonrecombining sex chromosome. We use individual-based simulations of a Muller's ratchet process to test this prediction, and investigate how the relevant parameters (effective population size, strength and dominance of deleterious mutations, size of nonrecombining segment, and strength of sexually antagonistic selection) are expected to affect the rate of turnovers. PMID:23461315

  1. Guide to good practices for operations turnover

    SciTech Connect

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Turnover, Chapter XII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing operations turnover programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Turnover is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for a formal operations turnover program to promote safe and efficient operations.

  2. Alcohol, signaling, and ECM turnover.

    PubMed

    Seth, Devanshi; D'Souza El-Guindy, Nympha B; Apte, Minoti; Mari, Montserrat; Dooley, Steven; Neuman, Manuela; Haber, Paul S; Kundu, Gopal C; Darwanto, Agus; de Villiers, Willem J; Vonlaufen, A; Xu, Z; Phillips, P; Yang, S; Goldstein, D; Pirola, R M; Wilson, J S; Moles, Anna; Fernández, Anna; Colell, Anna; García-Ruiz, Carmen; Fernández-Checa, José C; Meyer, Christoph; Meindl-Beinker, Nadja M

    2010-01-01

    Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis. This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse.

  3. The effect of interleukin-1alpha polymorphisms on bone mineral density and the risk of vertebral fractures.

    PubMed

    Knudsen, S; Harsløf, T; Husted, L B; Carstens, M; Stenkjaer, L; Langdahl, B L

    2007-01-01

    Interleukin-1alpha (IL-1alpha) stimulates bone resorption via osteoclasts. Mononuclear cells from patients with osteoporosis show increased IL-1alpha production, and IL-1alpha mRNA is more often detected in bone biopsies from osteoporotic compared to normal postmenopausal women. Polymorphisms have been identified in the IL-1alpha gene; however, none of these has been examined for an effect on bone phenotypes in Caucasians. We investigated if the polymorphisms in the IL-1alpha gene affect the risk of osteoporotic fractures, bone mineral density (BMD), and bone turnover in 462 osteoporotic patients and 336 normal controls. Based on previous studies of polymorphisms in the gene and data from the International Hap-Map Project, four polymorphisms needed examination in order to investigate the effect of known polymorphisms in the IL-1alpha gene. We examined C(-1202)-T(rs1800794), C(-889)-T(rs1800587), T(155 + 209)-C(rs2071373), C(155 + 320)-T(rs2856838), and G(398)-T(rs 17561) by Taqman and restriction fragment-length polymorphism assays. BMD was examined by dual-energy X-ray absorptiometry. Bone turnover was evaluated by serum osteocalcin, serum carboxy-terminal propeptide of human type I procollagen, serum bone-specific alkaline phosphatase, serum carboxy-terminal telopeptide of type I collagen, and urinary hydroxyproline/creatinine. Genotype distributions were in Hardy-Weinberg equilibrium. All polymorphisms were in strong linkage disequilibrium. The C allele of the C(155 + 320)-T polymorphism tended to be more common among patients with vertebral fractures (P = 0.06) and patients with BMD T score <-2.5 (P = 0.05). Furthermore, haplotype 1 was associated with reduced risk of having BMD T score <-2.5 (P = 0.02). None of the other polymorphisms or haplotypes was associated with fracture risk or BMD T score <-2.5. BMD and bone turnover were not associated with any of the genetic variants. In conclusion, all the polymorphisms within the IL-1alpha gene are in strong

  4. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone

    PubMed Central

    Zhong, Zhendong A.; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lane, Nancy E.; Yao, Wei

    2015-01-01

    The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR) knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1) and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis. PMID:26431032

  5. Validation of estimating food intake in gray wolves by 22Na turnover

    USGS Publications Warehouse

    DelGiudice, G.D.; Duquette, L.S.; Seal, U.S.; Mech, L.D.

    1991-01-01

    We studied 22sodium (22Na) turnover as a means of estimating food intake in 6 captive, adult gray wolves (Canis lupus) (2 F, 4 M) over a 31-day feeding period. Wolves were fed white-tailed deer (Odocoileus virginianus) meat only. Mean mass-specific exchangeable Na pool was 44.8 .+-. 0.7 mEq/kg; there was no differeence between males and females. Total exchangeable Na was related (r2 = 0.85, P < 0.009) to body mass. Overall, 22Na turnover overestimated Na intake by 9.8 .+-. 2.4% after 32 days. Actual Na intake was similar in males and females; however, Na turnover (P < 0.05) and the discrepancy (P < 0.01) between turnover and actual Na intake were greater in females than males. From Day 8 to the end of the study, the absolute difference (mEq) between Na intake and Na turnover remained stable. Sodium turnover (mEq/kg/day) was a reliable (r2 = 0.91, P < 0.001) estimator of food consumption (g/kg/day) in wolves over a 32-day period. Sampling blood and weighing wolves every 1-4 days permitted identification of several potential sources of error, including changes in size of exchangeable Na pools, exchange of 22Na with gastrointestinal and bone Na, and rapid loss of the isotope by urinary excretion.

  6. Bone histology in chronic kidney disease-related mineral and bone disorder.

    PubMed

    Kazama, Junichiro James

    2011-06-01

    A quantitative histological analysis of biopsied bone samples is currently regarded as the gold standard for a diagnosing procedure for bone diseases associated with chronic kidney disease-related mineral and bone disorder. Conventionally, "bone cell activities" and "bone mineralization" are applied as two independent assessment axes, and the histology results are classified into five categories according to these axes. Recently, a new bone histology classification system called the Turnover-Mineralization-Volume system, which applied "cancellous bone volume" as another major assessing axis, was advocated; however, both classification systems have many unsolved problems. Clinicians must realize the limitations in evaluating bone metabolism by bone histology. We will need to establish a new classification method for renal bone diseases independent of histological findings.

  7. The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Arnaud, Sara B.

    1995-01-01

    On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased

  8. The effect of 5alpha-reductase inhibition with finasteride and dutasteride on bone mineral density in older men with benign prostatic hyperplasia.

    PubMed

    Mačukat, Indira Radin; Spanjol, Josip; Orlič, Zeljka Crncevič; Butorac, Marta Zuvič; Marinovič, Marin; Ćupič, Dora Fučkar

    2014-09-01

    Testosterone is converted to dihyrotestosterone by two isoenzymes of 5alpha-reductase. Finasteride and dutasteride are 5alpha-reductase inhibitors commonly used in the treatment of benign prostatic hyperplasia. We compared indices of bone mineral density in 50 men treated with finasteride, 50 men treated with dutasteride and 50 men as control. Bone mineral density of spine and hip were measured using dual energy X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorptionby measuring serum C-terminal telopeptide of collagen type 1. In addition serum total testosteron and estradiol were determined. The dutasteride group had significantly higher mean bone min- eral density, mean bone mineral content, mean T score, mean Z score at femoral neck and mean total hip Z score than control. Mean total testosterone and estradiol levels were higher in the dutasteride group. There were no significant dif- ferences between the groups in lumbar spine bone density parameters or bone turnover markers. Our results provide evidence that long-term 5alpha-reductase suppression does not adversely affect bone mineral density. Dutasteride therapy could have beneficial effect on bone density. PMID:25507347

  9. The effect of 5alpha-reductase inhibition with finasteride and dutasteride on bone mineral density in older men with benign prostatic hyperplasia.

    PubMed

    Mačukat, Indira Radin; Spanjol, Josip; Orlič, Zeljka Crncevič; Butorac, Marta Zuvič; Marinovič, Marin; Ćupič, Dora Fučkar

    2014-09-01

    Testosterone is converted to dihyrotestosterone by two isoenzymes of 5alpha-reductase. Finasteride and dutasteride are 5alpha-reductase inhibitors commonly used in the treatment of benign prostatic hyperplasia. We compared indices of bone mineral density in 50 men treated with finasteride, 50 men treated with dutasteride and 50 men as control. Bone mineral density of spine and hip were measured using dual energy X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorptionby measuring serum C-terminal telopeptide of collagen type 1. In addition serum total testosteron and estradiol were determined. The dutasteride group had significantly higher mean bone min- eral density, mean bone mineral content, mean T score, mean Z score at femoral neck and mean total hip Z score than control. Mean total testosterone and estradiol levels were higher in the dutasteride group. There were no significant dif- ferences between the groups in lumbar spine bone density parameters or bone turnover markers. Our results provide evidence that long-term 5alpha-reductase suppression does not adversely affect bone mineral density. Dutasteride therapy could have beneficial effect on bone density. PMID:25420363

  10. Arachidonic acid enhances turnover of the dermal skeleton: studies on zebrafish scales.

    PubMed

    de Vrieze, Erik; Moren, Mari; Metz, Juriaan R; Flik, Gert; Lie, Kai Kristoffer

    2014-01-01

    In fish nutrition, the ratio between omega-3 and omega-6 poly-unsaturated fatty acids influences skeletal development. Supplementation of fish oils with vegetable oils increases the content of omega-6 fatty acids, such as arachidonic acid in the diet. Arachidonic acid is metabolized by cyclooxygenases to prostaglandin E2, an eicosanoid with effects on bone formation and remodeling. To elucidate effects of poly-unsaturated fatty acids on developing and existing skeletal tissues, zebrafish (Danio rerio) were fed (micro-) diets low and high in arachidonic acid content. Elasmoid scales, dermal skeletal plates, are ideal to study skeletal metabolism in zebrafish and were exploited in the present study. The fatty acid profile resulting from a high arachidonic acid diet induced mild but significant increase in matrix resorption in ontogenetic scales of adult zebrafish. Arachidonic acid affected scale regeneration (following removal of ontogenetic scales): mineral deposition was altered and both gene expression and enzymatic matrix metalloproteinase activity changed towards enhanced osteoclastic activity. Arachidonic acid also clearly stimulates matrix metalloproteinase activity in vitro, which implies that resorptive effects of arachidonic acid are mediated by matrix metalloproteinases. The gene expression profile further suggests that arachidonic acid increases maturation rate of the regenerating scale; in other words, enhances turnover. The zebrafish scale is an excellent model to study how and which fatty acids affect skeletal formation.

  11. Estimated lean mass and fat mass differentially affect femoral bone density and strength index but are not FRAX independent risk factors for fracture.

    PubMed

    Leslie, William D; Orwoll, Eric S; Nielson, Carrie M; Morin, Suzanne N; Majumdar, Sumit R; Johansson, Helena; Odén, Anders; McCloskey, Eugene V; Kanis, John A

    2014-11-01

    Although increasing body weight has been regarded as protective against osteoporosis and fractures, there is accumulating evidence that fat mass adversely affects skeletal health compared with lean mass. We examined skeletal health as a function of estimated total body lean and fat mass in 40,050 women and 3600 men age ≥50 years at the time of baseline dual-energy X-ray absorptiometry (DXA) testing from a clinical registry from Manitoba, Canada. Femoral neck bone mineral density (BMD), strength index (SI), cross-sectional area (CSA), and cross-sectional moment of iner